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Bays H, Pi-Sunyer X, Hemmingsson JU, Claudius B, Jensen CB, Van Gaal L. Liraglutide 3.0 mg for weight management: weight-loss dependent and independent effects. Curr Med Res Opin. 2017 Feb;33(2):225-229. doi: 10.1080/03007995.2016.1251892. PubMed PMID: 27817208.

Eckel RH, Bays HE, Klein S, Bade Horn D. Proactive and Progressive Approaches in Managing Obesity. Postgrad Med. 2016 Oct;128 Suppl 1:21-30. doi:
10.1080/00325481.2016.1181412. PubMed PMID: 27153316.

Bays H, Kothari SN, Azagury DE, Morton JM, Nguyen NT, Jones PH, Jacobson TA, Cohen DE, Orringer C, Westman EC, Horn DB, Scinta W, Primack C. Lipids and bariatric procedures Part 2 of 2: scientific statement from the American Society for Metabolic and Bariatric Surgery (ASMBS), the National Lipid Association (NLA), and Obesity Medicine Association (OMA). Surg Obes Relat Dis. 2016 Mar-Apr;12(3):468-95.

Abstract: Bariatric procedures generally improve dyslipidemia, sometimes substantially so. Bariatric procedures also improve other major cardiovascular risk factors. This 2-part Scientific Statement examines the lipid effects of bariatric procedures and reflects contributions from authors representing the American Society for Metabolic and Bariatric Surgery (ASMBS), the National Lipid Association (NLA), and the Obesity Medicine Association (OMA). Part 1 was published in the Journal of Clinical Lipidology, and reviewed the impact of bariatric procedures upon adipose tissue endocrine and immune factors, adipose tissue lipid metabolism, as well as the lipid effects of bariatric procedures relative to bile acids and intestinal microbiota. This Part 2 reviews: (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease (CVD) risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on CVD; and finally, (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies, that may occur after bariatric procedures.

Bays HE, Jones PH, Jacobson TA, Cohen DE, Orringer CE, Kothari S, Azagury DE, Morton J, Nguyen NT, Westman EC, Horn DB, Scinta W, Primack C. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: FULL REPORT. J Clin Lipidol. 2016 Jan-Feb;10(1):33-57.

Abstract: Bariatric procedures often improve lipid levels in patients with obesity. This 2 part scientific statement examines the potential lipid benefits of bariatric procedures and represents the contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on published data through June 2015. Part 1 of this 2 part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease (CVD) risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on CVD; and finally, (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the full report of part 1. (CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE)

Bays HE, Jones PH, Jacobson TA, Cohen DE, Orringer CE, Kothari S, Azagury DE, Morton J, Nguyen NT, Westman EC, Horn DB, Scinta W, Primack C. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: EXECUTIVE SUMMARY. J Clin Lipidol. 2016 Jan-Feb;10(1):15-32.

Bays H, Scinta W. Adiposopathy and epigenetics: an introduction to obesity as a transgenerational disease. Curr Med Res Opin. 2015 Nov;31(11):2059-69. (CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE)

Brown WV, Bays HE, La Forge R, Sikand G. JCL Roundtable: Gender differences in risk reduction with lifestyle changes. J Clin Lipidol. 2015 Jul-Aug;9(4):486-95.

Bays H: Central obesity as a clinical marker of adiposopathy; increased visceral adiposity as a surrogate marker for global fat dysfunction. Curr Opin Endocrinol Diabetes Obes 2014 21:345-351.

Brown WV, Bays H, Bray GA. JCL Roundtable: Clinical management of individuals with obesity. J Clin Lipidol. 2014 May - June;8(3):237-248. doi: 10.1016/j.jacl.2014.02.005. Epub 2014 Feb 15. Review. PubMed PMID: 24793344.

Bays H. Adiposopathy, "Sick Fat," Ockham's Razor, and Resolution of the Obesity Paradox. Curr Atheroscler Rep. 2014 May;16(5):409. doi: 10.1007/s11883-014-0409-1. PubMed PMID: 24659222. (CLICK HERE FOR FREE DOWNLOAD OF THIS ARTICLE)

Bays HE, Weinstein R, Law G, Canovatchel W. Canagliflozin, a sodium glucose co-transporter 2 inhibitor: effects in overweight and obese subjects without diabetes mellitus. Obesity (Silver Spring). 2013 Nov 13. doi: 10.1002/oby.20663. [Epub ahead of print]

Bays HE, Toth PP, Kris-Etherton PM, Abate N, Aronne LJ, Brown WV, Gonzalez-Campoy JM, Jones SR, Kumar R, La Forge R, Samuel VT. Obesity, adiposity, and dyslipidemia: A consensus statement from the National Lipid Association. J Clin Lipidol. 2013 Jul-Aug;7(4):304-83. doi: 10.1016/j.jacl.2013.04.001. Epub 2013 May 31

Abstract: The term "fat" may refer to lipids as well as the cells and tissue that store lipid (ie, adipocytes and adipose tissue). "Lipid" is derived from "lipos," which refers to animal fat or vegetable oil. Adiposity refers to body fat and is derived from "adipo," referring to fat. Adipocytes and adipose tissue store the greatest amount of body lipids, including triglycerides and free cholesterol. Adipocytes and adipose tissue are active from an endocrine and immune standpoint. Adipocyte hypertrophy and excessive adipose tissue accumulation can promote pathogenic adipocyte and adipose tissue effects (adiposopathy), resulting in abnormal levels of circulating lipids, with dyslipidemia being a major atherosclerotic coronary heart disease risk factor. It is therefore incumbent upon lipidologists to be among the most knowledgeable in the understanding of the relationship between excessive body fat and dyslipidemia. On September 16, 2012, the National Lipid Association held a Consensus Conference with the goal of better defining the effect of adiposity on lipoproteins, how the pathos of excessive body fat (adiposopathy) contributes to dyslipidemia, and how therapies such as appropriate nutrition, increased physical activity, weight-management drugs, and bariatric surgery might be expected to impact dyslipidemia. It is hoped that the information derived from these proceedings will promote a greater appreciation among clinicians of the impact of excess adiposity and its treatment on dyslipidemia and prompt more research on the effects of interventions for improving dyslipidemia and reducing cardiovascular disease risk in overweight and obese patients.

Hollander P, Gupta AK, Plodkowski R, Greenway F, Bays H, Burns C, Klassen P, Fujioka K; for the COR-Diabetes Study Group. Effects of Naltrexone Sustained- Release/Bupropion Sustained Release Combination Therapy on Body Weight and Glycemic Parameters in Overweight and Obese Patients With Type 2 Diabetes. Diabetes Care. 2013 Oct 21. [Epub ahead of print] PubMed PMID: 24144653.

Bays HE. Adiposopathy, diabetes mellitus, and primary prevention of atherosclerotic coronary heart disease: treating "sick fat" through improving fat function with antidiabetes therapies. Am J Cardiol 2012;110:4B-12B.

Bays HE, Gadde KM. Phentermine/topiramate for weight reduction and treatment of adverse consequences in obesity. Drugs Today. 2011;47:903-914.

Bays HE. Adiposopathy: Is "Sick Fat" a Cardiovascular Disease? Journal of the American College of Cardiology. 2011;57:2461-2473. (CLICK HERE FOR ONLINE MEDSCAPE REPRINT OF THIS ARTICLE)

Bays HE. Specialty Corner: Investigational Anti-obesity Agents to Treat Adiposopathy and "Sick Fat." Lipid Spin. Pages 22-23. 2011

Bays HE. Lorcaserin: drug profile and illustrative model of the regulatory challenges of weight-loss drug development. Expert Rev. Cardiovasc. Ther. 2011; 9(3), 265–277 (2011) (CLICK HERE FOR FREE DOWNLOAD OF THIS ARTICLE)

Abstract:Lorcaserin is a selective 5-hydroxytryptamine receptor 2c agonist developed as a weight-loss drug. Phase II and III clinical trials support lorcaserin as not only reducing adiposity (i.e., fat mass), but also as improving the metabolic diseases commonly associated with adiposopathy (i.e., fat dysfunction). At the time of this writing, regulatory processes continue towards evaluating lorcaserin as a potentially marketed weight-loss and weight-maintenance agent. Some of the challenges facing lorcaserin are similar to the difficulties encountered by all investigational weight loss therapeutic agents, which include evolving paths towards approval. While important for clinicians to understand approval hurdles for all therapeutics, it is especially critical for researchers and developers to grasp the unique regulatory complexities of anti-obesity agents. This article profiles lorcaserin as an illustrative example of general drug development regulatory processes, and specifically details the unique challenge of weight-loss drug development. [CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE, Gonzalez-Campoy JM, Schorr AB. What men should know about metabolic syndrome, adiposopathy, and "sick fat." Int J Clin Pract. 2010;64:1735-1739.

Bays H. Perspective: Is Bias Behind the Lack of New Obesity Drug Therapies? Clinical Endocrinology News. 5(8), 10- (2010).

Bays H. Phentermine, topiramate, and their combination for the treatment of adiposopathy ("sick fat") and metabolic disease. Expert Rev. Cardiovasc. Ther. 2010; 8(12):1777-801.

Abstract: Positive caloric balance often causes pathologic adipocyte and adipose tissue anatomical and functional changes (termed adiposopathy or 'sick fat'), which may lead to pathogenic adipocyte and adipose tissue responses and metabolic disease. Fat weight loss may improve adiposopathy, and thus improve metabolic disease in overweight patients. Unfortunately, the efficacy of nonsurgical weight loss therapies is often limited due to redundant physiological systems that help 'protect' against starvation and/or negative caloric balance. One strategy to overcome these limitations is to combine weight loss drug therapies having complementary mechanisms of action, thereby affecting more than one physiologic process influencing body fat accumulation. Phentermine is a noradrenergic sympathomimetic amine approved for short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide derivative of the naturally occurring sugar monosaccharide d-fructose approved as treatment for migraine headaches and seizure disorders. Although known to facilitate weight loss since its approval, topiramate monotherapy does not have a regulatory indication as an anti-obesity agent. Phentermine HCl / topiramate controlled-release (PHEN/TPM CR) is a combination agent containing immediaterelease phentermine and controlled-release topiramate. Clinical trials involving thousands of patients demonstrate PHEN/TPM CR to be effective in improving the weight of patients, and also effective in improving adiposopathy-associated metabolic diseases. This review examines the pathophysiology of adiposopathy as a contributor to metabolic disease, the data supporting phentermine monotherapy, topiramate monotherapy and their combination as anti-obesity and anti-adiposopathy agents, and the preliminary evidence supporting PHEN/TPM CR as a generally well-tolerated and effective agent to improve metabolic disease. [CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe, Bays H, Shanahan WR. and the Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group. Multicenter, Placebo-Controlled Trial of Lorcaserin for Weight Management N Engl J Med 2010 363;32:245-256

Bays HE. Faculty of 1000 Medicine, 29 July 2010 COMMENTARY
Magkos F, Fabbrini E, Mohammed BS, Patterson BW, Klein S. Increased whole-body adiposity without a concomitant increase in liver fat is not associated with augmented metabolic dysfunction. Obesity (Silver Spring). 2010 Aug;18(8):1510-5. Epub 2010 Apr 15.

Bays HE, Fox KM, Gandy S. Anthropometric Measurements and Diabetes Mellitus: Clues to the "Pathogenic" and "Protective" Potential of Adipose Tissue. Metab Synr Relat Disord. Metab Syndr Relat Disord. 2010 Aug;8(4):307-15.

Bays HE. Lorcaserin and adiposopathy: 5-HT2c agonism as a treatment for ‘sick fat’ and metabolic disease. Expert Rev. Cardiovasc. Ther. 7(11), 1429–1445 (2009)

Abstract: Agonists of 5-hydroxytryptamine (5-HT; serotonin) receptors promote loss of excessive body fat (adiposity) and improve metabolic parameters associated with adiposity-induced adipose tissue dysfunction (adiposopathy or ‘sick fat’). By improving adipose tissue pathogenic endocrine and immune responses in overweight patients, 5-HT receptor agonists may improve metabolic disease. Lorcaserin (APD-356) is a selective 5-HT2c receptor agonist that promotes weight loss. Probably owing to its selectivity for the 5-HT2c receptor, clinical trial evidence supports that lorcaserin does not adversely affect heart valves or pulmonary artery pressure. This review examines: the mechanisms by which serotonergic pathways improve adiposity and adiposopathy; historical data and perspective regarding the efficacy and safety of prior 5-HT agonists; speculation regarding future paradigms in treating adiposopathy; and why lorcaserin may prove to be a safe and generally well-tolerated agent that not only improves the weight of patients, but also improves the health of patients. [CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE, Bazata DD, Fox KM, Grandy G, Gavin JR, SHIELD Study Group. Perceived body image in men and women with type 2 diabetes mellitus: correlation of body mass index with the figure rating scale. Nutr J 2009 16;5:57

Bays HE, Laferrere B, Dixon J, Arrone L, Gonzalez-Campoy JM, Apovian C, Wolfe BM. "Adiposopathy and bariatric surgery: is 'sick fat' a surgical disease?" Consensus Paper. Int J Clin Pract Sept. 2009 63(9) 1285-1300

Objective: To review how bariatric surgery in obese patients may effectively treatadiposopathy (pathogenic adipose tissue or ‘sick fat’), and to provide clinicians arationale as to why bariatric surgery is a potential treatment option for overweightpatients with type 2 diabetes, hypertension, and dyslipidaemia. Methods: A groupof clinicians, researchers, and surgeons, all with a background in treating obesityand the adverse metabolic consequences of excessive body fat, reviewed the medicalliterature regarding the improvement in metabolic disease with bariatric surgery. Results: Bariatric surgery improves metabolic disease through multiple, likelyinterrelated mechanisms including: (i) initial acute fasting and diminished caloricintake inherent with many gastrointestinal surgical procedures; (ii) favourable alterationsin gastrointestinal endocrine and immune responses, especially with bariatricsurgeries that reroute nutrient gastrointestinal delivery such as gastric bypass procedures;and (iii) a decrease in adipose tissue mass. Regarding adipose tissuemass, during positive caloric balance, impaired adipogenesis (resulting in limitationsin adipocyte number or size) and visceral adiposity are anatomic manifestationsof pathogenic adipose tissue (adiposopathy). This may cause adverse adiposetissue endocrine and immune responses that lead to metabolic disease. A decreasein adipocyte size and decrease in visceral adiposity, as often occurs with bariatricsurgery, may effectively improve adiposopathy, and thus effectively treat metabolicdisease. It is the relationship between bariatric surgery and its effects upon pathogenicadipose tissue that is the focus of this discussion. Conclusions: In selectiveobese patients with metabolic disease who are refractory to medical management,adiposopathy is a surgical disease. [CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE. Faculty of 1000 Medicine, 01 Sept 2009 []: Cypess, A. M., Lehman, S., Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y. H., Doria, A., Kolodny, G. M., and Kahn, C. R. Identification and importance of brown adipose tissue in adult humans. N.Engl.J.Med. 360(15), 1509-1517 (4-9-2009)

Bays HE. "Sick fat," metabolic disease, and atherosclerosis. Am J Med. 2009; 122 (1 Suppl) S26-37.

Abstract: Atherosclerotic coronary heart disease (CHD) is the most common cause of morbidity and mortality among men and women in developed nations. The obesity epidemic contributes to the increasing prevalence of high blood sugar (as may be found in patients with diabetes mellitus and metabolic syndrome), high blood pressure, and dyslipidemia--all CHD risk factors. Metabolic syndrome describes the common clinical finding wherein component CHD risk factors cluster within a single patient, but this term does not identify any unified pathophysiologic process. However, a component of the metabolic syndrome is abdominal obesity, which does reflect an anatomic manifestation of a "common-soil" pathophysiologic process that promotes the onset of CHD risk factors, and thus increases CHD risk. Adiposopathy ("sick fat") is anatomically characterized by visceral adiposity and adipocyte hypertrophy; it is manifested physiologically by a net increase in release of free fatty acids and by pathogenic adipose tissue metabolic/immune responses that promote metabolic disease and increase CHD risk. Understanding the relation of adiposopathy to CHD risk factors and recognizing the importance of treating both the "cause and effect" of metabolic diseases are critical toward a comprehensive approach in reducing CHD risk. Regarding the "cause," clinicians and their patients should be diligent regarding appropriate nutritional and lifestyle interventions that may favorably affect health. Regarding the "effect," clinicians and their patients should be equally diligent toward appropriate pharmaceutical interventions that reduce CHD risk factors when nutritional and lifestyle interventions do not sufficiently achieve desired metabolic treatment goals. [CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE. Faculty of 1000 Medicine, 23 Feb 2009 [] : Hivert MF, Sullivan LM, Fox CS, Nathan DM, D'Agostino RB, Wilson PW, Meigs JB. Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance. J Clin Endocrinol Metab 2008 Aug 93(8):3165-72

Bays HE, Gonzalez-Campoy JM, Henry RR, Bergman DA, Schorr AB, Rodbard. Is adiposopathy ("sick fat") an endocrine disease? Consensus Paper. Int J Clin Pract. 2008:10:1474-83.

Abstract: OBJECTIVE: To review current consensus and controversy regarding whether obesity is a 'disease', examine the pathogenic potential of adipose tissue to promote metabolic disease and explore the merits of 'adiposopathy' and 'sick fat' as scientifically and clinically useful terms in defining when excessive body fat may represent a 'disease'. METHODS: A group of clinicians and researchers, all with a background in endocrinology, assembled to evaluate the medical literature, as it pertains to the pathologic and pathogenic potential of adipose tissue, with an emphasis on metabolic diseases that are often promoted by excessive body weight. RESULTS: The data support pathogenic adipose tissue as a disease. Challenges exist to convince many clinicians, patients, healthcare entities and the public that excessive body fat is often no less a 'disease' than the pathophysiological consequences related to anatomical abnormalities of other body tissues. 'Adiposopathy' has the potential to scientifically define adipose tissue anatomic and physiologic abnormalities, and their adverse consequences to patient health. Adiposopathy acknowledges that when positive caloric balance leads to adipocyte hypertrophy and visceral adiposity, then this may lead to pathogenic adipose tissue metabolic and immune responses that promote metabolic disease. From a patient perspective, explaining how excessive caloric intake might cause fat to become 'sick' also helps provide a rationale for patients to avoid weight gain. Adiposopathy also better justifies recommendations of weight loss as an effective therapeutic modality to improve metabolic disease in overweight and obese patients. CONCLUSION: Adiposopathy (sick fat) is an endocrine disease.[CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE, Gonzalez-Campoy JM, Bray GA, Kitabchi AE, Bergman DA, Schorr AB, Rodbard HW, Henry RR.  Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity.  Expert Rev Cardiovasc Ther. 2008;3:343-368.

Abstract:  When caloric intake exceeds caloric expenditure, the positive caloric balance and storage of energy in adipose tissue often causes adipocyte hypertrophy and visceral adipose tissue accumulation. These pathogenic anatomic abnormalities may incite metabolic and immune responses that promote Type 2 diabetes mellitus, hypertension and dyslipidemia. These are the most common metabolic diseases managed by clinicians and are all major cardiovascular disease risk factors. 'Disease' is traditionally characterized as anatomic and physiologic abnormalities of an organ or organ system that contributes to adverse health consequences.  Using this definition, pathogenic adipose tissue is no less a disease than diseases of other body organs. This review describes the consequences of pathogenic fat cell hypertrophy and visceral adiposity, emphasizing the mechanistic contributions of genetic and environmental predispositions, adipogenesis, fat storage, free fatty acid metabolism, adipocyte factors and inflammation. Appreciating the full pathogenic potential of adipose tissue requires an integrated perspective, recognizing the importance of 'cross-talk' and interactions between adipose tissue and other body systems. Thus, the adverse metabolic consequences that accompany fat cell hypertrophy and visceral adiposity are best viewed as a pathologic partnership between the pathogenic potential adipose tissue and the inherited or acquired limitations and/or impairments of other body organs. A better understanding of the physiological and pathological interplay of pathogenic adipose tissue with other organs and organ systems may assist in developing better strategies in treating metabolic disease and reducing cardiovascular disease risk.  [CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Bays HE.  Faculty of 1000 Medicine, 3 Jan 2008 [] : Flatt JP. Differences in Basal energy expenditure and obesity. Obesity (Silver Spring) 2007 Nov 15(11):2546-8

Bays HE, Rodbard RW, Schorr AB, González-Campoy JM. Treating Pathogenic Adipose Tissue (Adiposopathy) to Reduce Cardiovascular Disease Risk. Current Treatment Options in Cardiovascular Medicine 2007 9;259-271

Abstract:  Excessive adipose tissue is potentially pathogenic due to its mass effects and through adverse metabolic/immune responses, which may lead to cardiovascular disease risk factors (eg, type 2 diabetes mellitus, hypertension, dyslipidemia, and possibly atherosclerosis itself). Positive caloric balance in genetically/environmentally susceptible patients may result in adipocyte hypertrophy, visceral adipose tissue accumulation, and ectopic fat deposition, all causally associated with metabolic disease, and all anatomic manifestations of “adiposopathy” (a term used to describe adipose tissue pathology). Weight loss through improved nutrition, increased physical activity, and weight loss agents (ie, orlistat and sibutramine) improves adiposopathy and improves many metabolic diseases whose prevalence are directly associated with an increase in body fat and sedentary lifestyle. Cannabinoid receptor antagonists improve adiposopathy through weight reduction and favorable metabolic effects upon multiple body organs (including adipocytes). Peroxisome proliferator-activated receptor-γ agonists may improve adiposopathy through recruitment of functional fat cells and apoptosis of dysfunctional fat cells.

Bays HE. Faculty of 1000 Medicine, 16 Aug 2007 [] : Brücher R, Cifuentes M, Acuña MJ, Albala C, Rojas CV. Larger anti-adipogenic effect of angiotensin II on omental preadipose cells of obese humans. Obesity (Silver Spring) 2007 Jul 15(7):1643-6

Bays HE.  Faculty of 1000 Medicine, 21 Jun 2007 [] : Klein S, Allison DB, Heymsfield SB, Kelley DE, Leibel RL, Nonas C, Kahn R. Waist Circumference and Cardiometabolic Risk: a Consensus Statement from Shaping America's Health: Association for Weight Management and Obesity Prevention; NAASO, the Obesity Society; the American Society for Nutrition; and the American Diabetes Association. Obesity (Silver Spring) 2007 May 15(5):1061-7

Bays HE, Chapman RH, Grandy S.  The relationship of body mass index to diabetes mellitus, hypertension and dyslipidaemia: comparison of data from two national surveys.  Int J Clin Pract, May 2007, 61, 5, 737–747

Bays HE.  Faculty of 1000 Medicine, 11 Apr 2007 [] : Salans LB, Bray GA, Cushman SW, Danforth E, Glennon JA, Horton ES, Sims EA Glucose metabolism and the response to insulin by human adipose tissue in spontaneous and experimental obesity. Effects of dietary composition and adipose cell size. J Clin Invest 1974 Mar 53(3):848-56.  Faculty of 1000 Medicine.  2007

Erondu N, Wadden T, Gantz I, Musser B, Nguyen AM, Bays H, Bray G, O'neil PM, Basdevant A, Kaufman KD, Heymsfield SB, Amatruda JM: Effect of NPY5R Antagonist MK-0557 on Weight Regain after Very-low-calorie Diet-induced Weight Loss. Obesity 15:895-905, 2007

Bays H.  Adiposopathy—Defining, Diagnosing, and Establishing Indications to Treat ‘Sick Fat’: What Are the Regulatory Considerations?  US Endocrine Disease 2006  Issue 2 pages 12-14.

Bays H.  Adiposopathy:  The Endocannabinoid System as a Therapeutic Treatment Target for Dysfunctional Fat "Sick" Fat.  CJHP 19(1) 32-39 (2007)

Bays H, Blonde L, Rosenson R.  Adiposopathy:  how do diet, exercise, and weight loss drug therapies improve metabolic disease in overweight patients.  Expert Rev. Cardiovasc. Ther. 4(6), 871–895 (2006)  [CLICK HERE FOR A FREE DOWNLOAD OF THIS ARTICLE]

Abstract:  An increase in bodyweight is generally associated with an increased risk of excessive fat-related metabolic diseases (EFRMD), including Type 2 diabetes mellitus, hypertension and dyslipidemia. However, not all patients who are overweight have EFRMD, and not all patients with EFRMD are significantly overweight. The adipocentric paradigm provides the basis for a unifying, pathophysiological process whereby fat gain in susceptible patients leads to fat dysfunction (‘sick fat’), and wherein pathological abnormalities in fat function (adiposopathy) are more directly related to the onset of EFRMD than increases in fat mass (adiposity) alone. But just as worsening fat function worsens EFRMD, improved fat function improves EFRMD. Peroxisome proliferator-activated receptor-γ agonists increase the recruitment, proliferation and differentiation of preadipocytes (‘healthy fat’) and cause apoptosis of hypertrophic and dysfunctional (including visceral) adipocytes resulting in improved fat function and improved metabolic parameters associated with EFRMD. Weight loss interventions, such as a hypocaloric diet and physical exercise, in addition to agents such as orlistat, sibutramine and cannabinoid receptor antagonists, may have favorable effects upon fat storage (lipogenesis and fat distribution), nutrient metabolism (such as free fatty acids), favorable effects upon adipose tissue factors involved in metabolic processes and inflammation, and enhanced ‘cross-talk’ with other major organ systems. In some cases, weight loss therapeutic agents may even affect metabolic parameters and adipocyte function independently of weight loss alone, suggesting that the benefit of these agents in improving EFRMD may go beyond their efficacy in weight reduction. This review describes how adiposopathy interventions may affect fat function, and thus improve EFRMD.

Erondu N, Gantz I, Musser B, Suryawanshi S, Mallick M, Addy C, Cote J, Bray G, Fujioka K, Bays H, Hollander P, Sanabria-Bohorquez SM, Eng W, Langstrom B, Hargreaves RJ, Burns HD, Kanatani A, Fukami T, Macneil DJ, Gottesdiener KM, Amatruda JM, Kaufman KD, Heymsfield SB. Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults.  Cell Metab. 2006 Oct;4(4):275-82.

Bays H.  Commentary:  Adiposopathy causes the metabolic syndrome:  The beginning or end of a controversy?  Home of the International Atherosclerosis Society.  Posted Sept 2006

Bays H.  The Melanocortin System as a Therapeutic Treatment Target for Adiposity and Adiposopathy  Drugs R & D 2006; 7 (5): 289-302

Bays H, Ballantyne C.  Adiposopathy:  why do adiposity and obesity cause metabolic disease?  Future Lipidol. 2006 1(4), 389-420

Abstract: In the adipocentric paradigm, fat health affects patient health. Adiposopathy (‘pathos’ of adipose tissue or fat dysfunction) is more directly associated with excessive fat-related metabolic disease (EFRMD) than adiposity (increased fat mass) alone. Examples of adipocyte factors whose dysmetabolism may contribute to Type 2 diabetes mellitus include: 11 β-hydroxysteroid dehydrogenase type 1, acylation-stimulating protein, adiponectin, adipsin, angiotensinogen, autotaxin, ceramide, free fatty acids, hormone-sensitive lipase, interleukin-6, insulin-like growth factor-1, leptin, lipin, lysophospholipids, perilipin, phosphoenolpyrovate carboxykinase, plasminogen activator inhibitor-1, resistin, retinol-binding protein, tumor necrosis factor-α, visceral adipose tissue-derived serpin and visfatin. Excessive body fat may lead to hypertension due to physical compression of kidneys, sleep apnea, and other mechanisms. Examples of adipocyte factors whose dysmetabolism may contribute to hypertension include: 11 β-hydroxysteroid dehydrogenase type 1, adiponectin, angiotensinogen, angiotensin I and II, angiotensin-converting enzyme, renin, cathepsin, chymase, free fatty acids, interleukin-6 and leptin. Examples of adipocyte factors whose dysmetabolism may contribute to dyslipidemia include: 11 β-hydroxysteroid dehydrogenase type 1, acylation-stimulating protein, adipophilin, adiponectin, adipsin, cholesteryl ester-transfer protein, free fatty acids, hormone-sensitive lipase, leptin, lipoprotein lipase, perilipin, phospholipid transfer protein, sex hormones and tumor necrosis factor-α. Numerous other adipocyte factors may directly affect atherosclerosis and cardiomyopathy. A better understanding and recognition of how fat weight gain contributes to EFRMD will substantially affect the research and development of therapeutic interventions that may treat or prevent adiposopathy, and dramatically influence which patients with EFRMD are best treated and how.

Bays HE, Dujovne CA.  Adiposopathy is a More Rational Treatment Target for Metabolic Disease Than Obesity Alone.  Current Atherosclerosis Reports 2006, 8:144–156

Abstract:  Current guidelines recommend that weight-loss therapy should be primarily based upon specific body mass index (BMI) cut-off limits. However, in the adipocentric paradigm, it is acknowledged that co-morbidities, such as type 2 diabetes mellitus, hypertension, and dyslipidemia, occur at all levels of BMI.  Excessive fat mass (adiposity) in genetically susceptible individuals results in fat dysfunction (adiposopathy), which then contributes to metabolic disorders that increase the risk of atherosclerotic cardiovascular disease. In this paradigm, the term “anti-obesity” treatment might best be replaced by “anti-adiposopathy” treatment, wherein the focus is not based solely on BMI, but instead directed towards physiologically improving fat cell function and clinically improving the metabolic health of patients. This may occur through appropriate diet, physical exercise, and other lifestyle changes, and/or from drug therapies. Cannabinoid receptor antagonists and peroxisome proliferator activated receptor agonists are examples of agents that physiologically improve fat function and clinically improve metabolic disease.

Bays H. A Novel Paradigm – Adiposopathy: The Next Big Thing? [essay].  American College of Cardiology Foundation; Cardiosource Website,  Jun 2005. Available at Accessed on June 29, 2005

Bays HE.  Adiposopathy, metabolic syndrome, quantum physics, general relativity, chaos and the Theory of Everything.  Expert Rev. Cardiovasc. Ther. 3(3), 393–404 (2005)

Abstract:  Excessive fat (adiposity) and dysfunctional fat (adiposopathy) constitute the most common worldwide epidemics of our time – and perhaps of all time. Ongoing efforts to explain how the micro (adipocyte) and macro (body organ) biologic systems interact through function and dysfunction in promoting Type 2 diabetes mellitus, hypertension and dyslipidemia are not unlike the mechanistic and philosophical thinking processes involved in reconciling the micro (quantum physics) and macro (general relativity) theories in physics. Currently, the term metabolic syndrome refers to a constellation of consequences often associated with excess body fat and is an attempt to unify the associations known to exist between the four fundamental metabolic diseases of obesity, hyperglycemia (including Type 2 diabetes mellitus), hypertension and dyslipidemia. However, the association of adiposity with these metabolic disorders is not absolute and the metabolic syndrome does not describe underlying causality, nor does the metabolic syndrome necessarily reflect any reasonably related pathophysiologic process. Just as with quantum physics, general relativity and the four fundamental forces of the universe, the lack of an adequate unifying theory of micro causality and macro consequence is unsatisfying, and in medicine, impairs the development of agents that may globally improve both obesity and obesity-related metabolic disease. Emerging scientific and clinical evidence strongly supports the novel concept that it is not adiposity alone, but rather it is adiposopathy that is the underlying cause of most cases of Type 2 diabetes mellitus, hypertension and dyslipidemia. Adiposopathy is a plausible Theory of Everything for mankind’s greatest metabolic epidemics.

Bays HE.  Adiposopathy: role of adipocyte factors in a new paradigm Expert Rev. Cardiovasc. Ther. 3;2:187-189 (2005)

Bays H, Abate N, Chandalia M.  Adiposopathy:  Sick Fat Causes High Blood Sugar, High Blood Pressure, and Dyslipidemia.  Future Cardiology (2005) 1(1), 39-59.

Abstract:  Adiposopathy is defined as pathological adipose tissue function that may be promoted and exacerbated by fat accumulation (adiposity) and sedentary lifestyle in genetically susceptible patients. Adiposopathy is a root cause of some of the most common metabolic diseases observed in clinical practice, including Type 2 diabetes mellitus, hypertension and dyslipidemia. The most common term for the metabolic consequences of adiposopathy is currently ‘the metabolic syndrome’. Drug usage to treat the metabolic syndrome has focused on the safety and efficacy of treatments directed towards individual components of the metabolic syndrome, and not so much upon adiposopathy itself. However, enough is known about the pathophysiology of adiposopathy to propose diagnostic criteria. Regulatory issues are important obstacles to the research and development of new drug treatments for the metabolic syndrome. It is hoped that these obstacles can, to some extent, be addressed and overcome by clearly defining and increasing our understanding of adiposopathy.

Bays HE.  Current and Investigational Anti-Obesity Agents and Obesity Therapeutic Treatment Targets.  Obesity Research 2004; Vol. 12 No. 8:1197-1211.

Abstract:  Public health efforts and current antiobesity agents have not controlled the increasing epidemic of obesity. Investigational antiobesity agents consist of 1) central nervous system agents that affect neurotransmitters or neural ion channels, including antidepressants (bupropion), selective serotonin 2c receptor agonists, antiseizure agents (topiramate, zonisamide), some dopamine antagonists, and cannabinoid-1 receptor antagonists (rimonabant); 2) leptin/insulin/central nervous system pathway agents, including leptin analogues, leptin transport and/or leptin receptor promoters, ciliary neurotrophic factor (Axokine), neuropeptide Y and agouti-related peptide antagonists, proopiomelanocortin and cocaine and amphetamine regulated transcript promoters, alpha-melanocyte-stimulating hormone analogues, melanocortin-4 receptor agonists, and agents that affect insulin metabolism/activity, which include protein-tyrosine phosphatase-1B inhibitors, peroxisome proliferator activated receptor- receptor antagonists, short-acting bromocriptine (ergoset), somatostatin agonists (octreotide), and adiponectin; 3) gastrointestinal-neural pathway agents, including those that increase cholecystokinin activity, increase glucagon-like peptide-1 activity (extendin 4, liraglutide, dipeptidyl peptidase IV inhibitors), and increase protein YY3-36 activity and those that decrease ghrelin activity, as well as amylin analogues (pramlintide); 4) agents that may increase resting metabolic rate (“selective” beta-3 stimulators/agonist, uncoupling protein homologues, and thyroid receptor agonists); and 5) other more diverse agents, including melanin concentrating hormone antagonists, phytostanol analogues, functional oils, P57, amylase inhibitors, growth hormone fragments, synthetic analogues of dehydroepiandrosterone sulfate, antagonists of adipocyte 11-Beta-hydroxysteroid dehydrogenase type 1 activity, corticotropinreleasing hormone agonists, inhibitors of fatty acid synthesis, carboxypeptidase inhibitors, indanones/indanols, aminosterols, and other gastrointestinal lipase inhibitors (ATL962). Finally, an emerging concept is that the development of antiobesity agents must not only reduce fat mass (adiposity) but must also correct fat dysfunction (adiposopathy).

Bays H, Shepherd J.  Diabetes, Metabolic Syndrome and Dyslipidemia.  Management Strategies in Diabetes.  Cambridge Medical Publications.  ISBN 0 904052 88 5.  (2004) 1 - 28.

Deedwania PC, Hunninghake DB, Bays HE,  Jones PH, Cain VA, Blasetto JW, for the STELLAR Study Group.  Effects of Rosuvastatin, Atorvastatin, Simvastatin, and Pravastatin on the Atherogenic Dyslipidemia of Patients with Characteristics of the Metabolic Syndrome.  The Am J Cardiol 2005 Feb 1; 95(3) 360-6.

Bays HE.  Metabolic Sydrome:  What might be occurring?  Managed Care Supplement.  October 2004 Vol. 13 No 10.  Pages 13-16.

Deedwania PC, Hunninghake DB, Bays HE  Effects of lipid-altering treatment in diabetes mellitus and the metabolic syndrome.  Am J Cardiol - 3-JUN-2004; 93(11A): 18C-26C.

Bays H, Mandarino L, DeFronzo RA.  Role of the Adipocyte, FFA, and Ectopic Fat in Pathogenesis of Type 2 Diabetes Mellitus.  Journal of Clinical Endocrinology and Metabolism 2004 89: 463-478.

Bays HE, McGovern ME.  Once-Daily Niacin Extended-Release/Lovastatin Combination Tablet has More Favorable Effects on Lipoprotein Particle Size and Subclass Distribution Compared to Atorvastatin and Simvastatin.  Preventive Cardiology. 2003;6:179-188  (Discusses the therapeutic effects of lipid-altering drugs in a patient population consistent with metabolic syndrome.)

Bays HE.  Atherogenic Dyslipidaemia in Type 2 Diabetes and Metabolic Syndrome: Current and Possible Future Treatment OptionsBr. J Diabetes Vasc Dis 2003;3(5)356-360

Bays HE, Stein EA.  Pharmacotherapy for Dyslipidemia - Current Therapies and Future Agents.  Expert Opinion on Pharmacotherapy. 2003, vol. 4, no. 11, pp. 1901 - 1938 (includes an "Expert Opinion" section on anti-obesity drug development)

Bays HE, Dujovne CA. Anti-obesity drug development. Expert Opin. Investig. Drugs (2002) 11(9):1189-1204.

Keywords:    anesthesia, anaesthesia, appetite, heart valve, obesity, obesity guideline, obesity metabolic cycle, resting metabolic rate, satiety, CNTF, ciliary neurotrophic factor, axokine, cannabinoid antagoinist, rimonabant, bupropion, P57, dopamine antagonist, risperidone, selective 5-HT 2c agonist, topiramate, domamine uptake inhibitor, norepinephrine uptake inhibitor, MC4R agonist / analogue, alpha MSH agonist / analogue, alpha melanocyte stimulating hormone agonist / analogue, AgRP inhibitor / antagonist, Agouti-related peptide, MCH antagonist, melanin concentrating hormone antagonist, NPY antagonist, Y1 antagonist, Y5 antagonist, neuropeptide Y antagonist, adipocyte complement-related protein of 30 KDa (Acrp30 / adiponectin), selective beta 3 receptor stimulator, beta agonist, thyroid receptor agonist, leptin analogue, CCK-A promoter, cholecystokinin-A promoter, glucagon-like peptide-1, lipase inhibitor, phytostanol, ghrelin antagonist, PPY3-36, protein tyrosine phosphatase drugs, peroxisome proliferator activator gamma receptor antagonist, short-acting bromocryptine, carboxypeptidase inhibitor, somatostatin agonist, octreotide, growth hormone fragments.

Bays HE, Dujovne CA. Pharmacotherapy of obesity. Currently marketed and upcoming agents. Am J. Cardiovascular Drugs. 2002;2(4):245-253.




Vanita R. Aroda, Julio Rosenstock, Joanna Uddén Hemmingsson, Melanie Davies, Trine V. Skjøth, Birgitte Claudius, Harold Bays  307-LB - Liraglutide 3.0 mg Efficacy and Safety by Baseline BMI in the SCALE Diabetes Trial: Post-hoc Analysis.  American Diabetes Association Annual Session.  June 5 - 9, 2015, Boston, Massachusetts. USA

Vanita R. Aroda, Julio Rosenstock, Joanna Uddén Hemmingsson, Melanie Davies, Trine V. Skjøth, Birgitte Claudius, Harold Bays  307-LB - Liraglutide 3.0 mg Efficacy and Safety by Baseline BMI in the SCALE Diabetes Trial: Post-hoc Analysis.  European Association for the Study of Obesity September 14 - 18 2015, Stockholm Sweden - Encore presentation.

Harold Edward Bays MD, F Xavier Pi-Sunyer, MD, MPH, Joanna Uddén Hemmingsson, MD, PhD, Christine Bjørn Jensen, MD, PhD, Birgitte Claudius, MD and Luc F Van Gaal, MD. PhD. Liraglutide 3.0 Mg: Weight-Loss Dependent and Independent Effects. Poster Board FRI-551. The Endocrine Society 97 Annual Meeting. March 5 - 8 2015. San Diego California USA.

Harold E. Bays, MD, Christie M. Ballantyne, MD, Rene A. Braeckman, PhD, William G. Stirtan, PhD, Paresh N. Soni, MD, PhD. Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) Therapy in Hypertriglyceridemic Stable-Statin–Treated Patients With Metabolic Syndrome: Effect on High-sensitivity C-reactive Protein Levels. Presented at the Annual Scientific Sessions of the Obesity Society (TOS), November 12–16, 2013, Atlanta, GA, USA.

Bays H. Fox KM, Grandy S. Adiposity, Age, and Family History as a Simplified Prediciton of Future Diabetes Mellitus from the SHIELD Study. Abstract 810-P. Obesity 29th Annual Scientific Meeting. Orlando Florida October 1-5, 2012.

Bays H, Schwartz S, Greenway F, Clapper B, Wang W, Kim D, Dunayevich E. Naltrexone SR/Bupropion SR Therapy in Overweight/Obese Subjects with Type 2 Diabetes Mellitus: Effects on Glycemic Control after Accounting for the Influence of Rescue Medications for Hyperglycemia. Abstract 1866 Guided Audio Poster Presentation. American Diabetes Association 71 nd Scientific Session June 24-28, 2011 San Diego California USA

Bays HE, Fox KM, Grandy S. Perceived Body Image for Optimal Health: Analysis of Racial Differences. Abstract Publication. 333-P. Obesity 2010 28th Annual Scientific Meeting. San Diego, California USA October 8 - 12, 2010

Alok K. Gupta, Priscilla Hollander, Harold Bays, Maria Guttadauria, Janelle Erickson, Dennis Kim, Eduardo Dunayevich. Improved Glycemic Control and Weight Loss with Naltrexone SR/Bupropion SR Combination Therapy in Overweight/Obese Subjects with Type 2 Diabetes. Abstract Publication. 2633−PO. American Diabetes Association. 70th Scientific Session. June 25-29 2010 Orlando Florida. USA

Bays H, Bazata DD, Fox KM, Grandy S. Differences in Perceived Body Image: Self-Image Versus Self-Identified Ideal Body Image: Men Versus Women. Abstract / Poster 2009 Annual Meeting of The Obesity Society. Washington DC. USA October 25, 2009

Bays HE, Bazata DD, Fox KM, Grandy S, Gavin JR. Perceived Body Image in Men and Women with Type 2 Diabetes Mellitus: Correlation of Figure Rating Scale with BMI. Poster. 2008 Annual Meeting of The Obesity Society, Phoenix, AZ USA, October 4, 2008.

Davidson MH, McKenney JM, Bays HE, Shentu Y, Lu K, Suryawanshi S, Heymsfield SB, Evans JK, Cruz S, Erondu N, Amatruda JM, Harp JB. The efficacy and tolerability of taranabant, a cannabinoid receptor inverse agonist, over 24 weeks in obese patients. Poster. 57th annual scientific session of the 16th European Congress on Obesity (ECO) in Geneva Switzerland, May 14th-17th, 2008.

Bays H, Fox K, Grandy S.  Waist Circumference, Hip Circumference, Body Mass Index (BMI), and Ratios:  Which Best Predicts Type 2 Diabetes Mellitus (T2DM) in Men and Women? Oral/Podium Presentation  Abstract 145-OR  The Obesity Society 2007 Annual Scientific Meeting  October 2 - 24, 2007 New Orleans Louisiana. USA 

Bays HE, Rodbard HW, Fox KM, Grandy S.  Changes in Weight, BMI, and Waist Circumference after 2 Years in Respondents with or at Risk for Metabolic Disease: Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD)  World Congress on Insulin Resistance Syndrome.  Poster presentation.  Boston Massachusetts October 11, 2007.

Bays H, Chapman R, Klingman D, Fanning K, Grandy S.  High Prevalence of Misdiagnosis of the Metabolic Syndrome in a Self-Reported Survey:  Possible Confusion with Having "a Metabolism Problem."  Poster.  Abstract 605.  October 22, 2006.  NAASO 2006 Annual Meeting.  Boston Massachusetts USA

Erondu N, Wadden T, Gantz I, Musser B, Nguyen AM, Bays H, Bray G, O'Neil  PM, Basdevant A, Kaufman K, Heymsfield S, Amatruda J.  Effect of NPY5R Antagonist MK-0557 on Weight Regain after VLCD-Induced Weight Loss.  Oral Presentation by Dr. Erondu.  Abstract 57.  October 22, 2006.  NAASO 2006 Annual Meeting.  Boston Massachusetts USA

Bays H, SHIELD Study Group.  BMI and Frequency of Diabetes, Hypertension, and Dyslipidemia:  Comparison of SHIELD AND NHANES Data.  Poster Abstract 488-P.  NAASO's 2005 Annual Meeting.  October 15-19, 2005 Vancouver, British Columbia, Canada

Weinstein SP, Tardiff BE, Bays HE, Guler HP, Aronne LJ.  Weight Loss with Recombinant Human Variant Ciliary Neurotrophic Factor (CNTF [AXOKINE]) Improves Glycemic Control in Overweight/Obese Subjects, Especially in Those with Abnormal Glycemic Parameters at Baseline  Diabetes 2004.  Supplement.  Abstract Publication Number:  2523-PO  64th Scientific Sessions

Glicklich A, Bays H, Russell T, Weinstein S, Hollander P.  AXOKINE Ò Promotes Weight Loss in Overweight and Obese Patients with Type 2 Diabetes Mellitus.  Poster Abstract 471-P.  NAASO's 2003 Annual Meeting.  October 11-15, 2003  Ft. Lauderdale Florida USA



Bays HE, Gonzalez-Campoy M.  Adiposopathy.  New-Opathies: - An Emerging Molecular Reclassification of Human Disease Textbook. Editor Errol C. Friedberg et. al. Copyright Chapter 4 Pages 105 - 168. 2012 by World Scientific Publishing Co. Pte. Ltd. ISBN-13:978-9814355681.