Diretrizes e Referências Bibliográficas em Medicina da Obesidade

AACE guidelines: Timothy Garvey, MD, FACE; Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU; Elise M. Brett, MD, FACE, CNSC, ECNU; Alan J. Garber, MD, PhD, FACE; Daniel L. Hurley, MD, FACE; Ania M. Jastreboff, MD, PhD; Karl Nadolsky, DO; Rachel Pessah-Pollack, MD; Raymond Plodkowski, MD; and Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines


Adult OMA Obesity guidelines:

Obesity Algorithm®

Bays HE, McCarthy W, Christensen S, Tondt J, Karjoo S, Davisson L, Ng J, Golden A, Burridge K, Conroy R, Wells S, Umashanker D, Afreen S, DeJesus R, Salter D, Shah N, Richardson L. Obesity Algorithm eBook, presented by the Obesity Medicine Association. www.obesityalgorithm.org. 2020. https://obesitymedicine.org/obesity-algorithm/

Exercise – ACSM guidelines


Obesity Management – ACC/AHA/TOS guidelines: Michael D. Jensen, Donna H. Ryan, Caroline M. Apovian, Jamy D. Ard, Anthony G. Comuzzie, Karen A. Donato, Frank B. Hu, Van S. Hubbard, John M. Jakicic, Robert F. Kushner, Catherine M. Loria, Barbara E. Millen, Cathy A. Nonas, F. Xavier Pi-Sunyer, June Stevens, Victor J. Stevens, Thomas A. Wadden, Bruce M. Wolfe, Susan Z. Yanovski


Pediatric Obesity—Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline: Dennis M. Styne, Silva A. Arslanian, Ellen L. Connor, Ismaa Sadaf Farooqi, M. Hassan Murad, Janet H. Silverstein, Jack A. Yanovski. J Clin Endocrinol Metab (2017) 102 (3): 709-757.


Pediatric OMA guidelines:

Pediatric Obesity Algorithm®

Cuda S, Censani M, Joseph M, Browne N, O’Hara V. Pediatric Obesity Algorithm, presented by the Obesity Medicine Association. 2018-2020.   



Pharmacotherapy – Endocrine Society Pharmacologic Management of Obesity guidelines: Caroline M. Apovian Louis J. Aronne Daniel H. Bessesen Marie E. McDonnell M. Hassan Murad Uberto Pagotto Donna H. Ryan Christopher D. Still


Surgery – AACE/TOS/ASMBS Guidelines 2013: Jeffrey I. Mechanick, M.D., Adrienne Youdim, M.D., Daniel B. Jones, M.D., M.S.,W., Timothy Garvey, M.D., Daniel L. Hurley, M.D., M. Molly McMahon, M.D., Leslie J. Heinberg, Ph.D., Robert Kushner, M.D., Ted D. Adams, Ph.D., M.P.H., Scott Shikora, M.D., John B. Dixon, M.B.B.S., Ph.D., Stacy Brethauer, M.D.


The USPSTF Pediatric Guidelines (June 2017)



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Chronic Disease of Obesity

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Fat Mass Disease

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76. Smith KB, Smith MS: Obesity Statistics. Prim Care 2016 43:121-135, ix. https://www.ncbi.nlm.nih.gov/pubmed/26896205

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78. Yu E, Ley SH, Manson JE, et al.: Weight History and All-Cause and Cause-Specific Mortality in Three Prospective Cohort Studies. Ann Intern Med 2017 166:613-620.

79. Caleyachetty R, Thomas GN, Toulis KA, et al.: Metabolically Healthy Obese and Incident Cardiovascular Disease Events Among 3.5 Million Men and Women. J Am Coll Cardiol 2017 70:1429-1437. https://www.ncbi.nlm.nih.gov/pubmed/28911506

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Behavioral Therapy

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Technologies for Weight Management

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353. Chou WY, Prestin A, Kunath S: Obesity in social media: a mixed methods analysis. Transl Behav Med 2014 4:314-323. https://www.ncbi.nlm.nih.gov/pubmed/25264470

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Functional Foods, Supplements, and Over-the-counter Therapies

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Obesity and Metabolic Disease

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449. Salazar J, Luzardo E, Mejias JC, et al.: Epicardial Fat: Physiological, Pathological, and Therapeutic Implications. Cardiol Res Pract 2016 2016:1291537. https://www.ncbi.nlm.nih.gov/pubmed/27213076

450. Cavender MA, Norhammar A, Birkeland KI, et al.: SGLT-2 Inhibitors and Cardiovascular Risk: An Analysis of CVD-REAL. J Am Coll Cardiol 2018 71:2497-2506. https://www.ncbi.nlm.nih.gov/pubmed/29852973

451. Kosiborod M, Lam CSP, Kohsaka S, et al.: Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL 2 Study. J Am Coll Cardiol 2018 71:2628-2639. https://www.ncbi.nlm.nih.gov/pubmed/29540325

452. Home P: Cardiovascular outcome trials of glucose-lowering medications: an update. Diabetologia 2019 https://www.ncbi.nlm.nih.gov/pubmed/30607467

453. Coulter AA, Rebello CJ, Greenway FL: Centrally Acting Agents for Obesity: Past, Present, and Future. Drugs 2018 78:1113-1132. https://www.ncbi.nlm.nih.gov/pubmed/30014268

454. Bohula EA, Wiviott SD, McGuire DK, et al.: Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients. N Engl J Med 2018 379:1107-1117. https://www.ncbi.nlm.nih.gov/pubmed/30145941

455. Bohula EA, Scirica BM, Inzucchi SE, et al.: Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61): a randomised, placebo-controlled trial. Lancet 2018 392:2269-2279. https://www.ncbi.nlm.nih.gov/pubmed/30293771

456. Bays H, Perdomo C, Nikonova E, et al.: Lorcaserin and metabolic disease: weight-loss dependent and independent effects. Obes Sci Pract 2018 4:499-505. https://www.ncbi.nlm.nih.gov/pubmed/30574343

457. Scirica BM, Bohula EA, Dwyer JP, et al.: Lorcaserin and Renal Outcomes in Obese and Overweight Patients in the CAMELLIA-TIMI 61 Trial. Circulation 2018 https://www.ncbi.nlm.nih.gov/pubmed/30586726

458. Gadde KM, Martin CK, Berthoud HR, et al.: Obesity: Pathophysiology and Management. J Am Coll Cardiol 2018 71:69-84. https://www.ncbi.nlm.nih.gov/pubmed/29301630

459. Ritchey ME, Harding A, Hunter S, et al.: Cardiovascular Safety During and After Use of Phentermine and Topiramate. J Clin Endocrinol Metab 2019 104:513-522. https://www.ncbi.nlm.nih.gov/pubmed/30247575

460. Das SR, Everett BM, Birtcher KK, et al.: 2018 ACC Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol 2018 72:3200-3223. https://www.ncbi.nlm.nih.gov/pubmed/30497881

461. Kramer CK, Ye C, Campbell S, et al.: Comparison of New Glucose-Lowering Drugs on Risk of Heart Failure in Type 2 Diabetes: A Network Meta-Analysis. JACC Heart Fail 2018 6:823-830. https://www.ncbi.nlm.nih.gov/pubmed/30196071

462. Sanches Machado d’Almeida K, Ronchi Spillere S, Zuchinali P, et al.: Mediterranean Diet and Other Dietary Patterns in Primary Prevention of Heart Failure and Changes in Cardiac Function Markers: A Systematic Review. Nutrients 2018 10: https://www.ncbi.nlm.nih.gov/pubmed/29320401

463. Jorsal A, Kistorp C, Holmager P, et al.: Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail 2017 19:69-77. https://www.ncbi.nlm.nih.gov/pubmed/27790809

464. Retwinski A, Kosmalski M, Crespo-Leiro M, et al.: The influence of metformin and the presence of type 2 diabetes mellitus on mortality and hospitalisation in patients with heart failure. Kardiol Pol 2018 76:1336-1343. https://www.ncbi.nlm.nih.gov/pubmed/29862487

465. Weir DL, Abrahamowicz M, Beauchamp ME, et al.: Acute vs cumulative benefits of metformin use in patients with type 2 diabetes and heart failure. Diabetes Obes Metab 2018 20:2653-2660. https://www.ncbi.nlm.nih.gov/pubmed/29934961

466. Margulies KB, Hernandez AF, Redfield MM, et al.: Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. JAMA 2016 316:500-508. https://www.ncbi.nlm.nih.gov/pubmed/27483064

467. Margulies KB, McNulty SE, Cappola TP: Lack of Benefit for Liraglutide in Heart Failure-Reply. JAMA 2016 316:2429-2430. https://www.ncbi.nlm.nih.gov/pubmed/27959992

468. Vorsanger MH, Subramanyam P, Weintraub HS, et al.: Cardiovascular Effects of the New Weight Loss Agents. J Am Coll Cardiol 2016 68:849-859.

469. Bethel MA, Patel RA, Merrill P, et al.: Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis. Lancet Diabetes Endocrinol 2018 6:105-113.

470. Sharma A, Cooper LB, Fiuzat M, et al.: Antihyperglycemic Therapies to Treat Patients With Heart Failure and Diabetes Mellitus. JACC Heart Fail 2018 6:813-822. Additional references used in this section: [4][21][30][75][87][365][366]

Obesity and Elevated Blood Sugar

471. 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 2006 4:871-895. https://www.ncbi.nlm.nih.gov/pubmed/17173503

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

473. Bays H, Abate N, Chandalia M: Adiposopathy: sick fat causes high blood sugar, high blood pressure and dyslipidemia. Future Cardiol 2005 1:39-59. https://www.ncbi.nlm.nih.gov/pubmed/19804060

474. Bays H: Adiposopathy, metabolic syndrome, quantum physics, general relativity, chaos and the Theory of Everything. Expert Rev Cardiovasc Ther 2005 3:393-404. https://www.ncbi.nlm.nih.gov/pubmed/15889967

475. Yu JS, Cui W: Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination. Development 2016 143:3050-3060. https://www.ncbi.nlm.nih.gov/pubmed/27578176

476. Makki K, Froguel P, Wolowczuk I: Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm 2013 2013:139239. https://www.ncbi.nlm.nih.gov/pubmed/24455420

477. DeMarco VG, Aroor AR, Sowers JR: The pathophysiology of hypertension in patients with obesity. Nat Rev Endocrinol 2014 10:364-376. https://www.ncbi.nlm.nih.gov/pubmed/24732974

478. Zoller V, Funcke JB, Keuper M, et al.: TRAIL (TNF-related apoptosis-inducing ligand) inhibits human adipocyte differentiation via caspase-mediated downregulation of adipogenic transcription factors. Cell Death Dis 2016 7:e2412.

479. Fronczyk A, Moleda P, Safranow K, et al.: Increased concentration of C-reactive protein in obese patients with type 2 diabetes is associated with obesity and presence of diabetes but not with macrovascular and microvascular complications or glycemic control. Inflammation 2014 37:349-357. https://www.ncbi.nlm.nih.gov/pubmed/24197824

480. D’Souza A M, Neumann UH, Glavas MM, et al.: The glucoregulatory actions of leptin. Mol Metab 2017 6:1052-1065. https://www.ncbi.nlm.nih.gov/pubmed/28951828

481. Geer EB, Islam J, Buettner C: Mechanisms of glucocorticoid-induced insulin resistance: focus on adipose tissue function and lipid metabolism. Endocrinol Metab Clin North Am 2014 43:75-102. https://www.ncbi.nlm.nih.gov/pubmed/24582093

482. Fisette A, Lapointe M, Cianflone K: Obesity-inducing diet promotes acylation stimulating protein resistance. Biochem Biophys Res Commun 2013 437:403-407. https://www.ncbi.nlm.nih.gov/pubmed/23831465

483. Thorp AA, Schlaich MP: Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome. J Diabetes Res 2015 2015:341583. https://www.ncbi.nlm.nih.gov/pubmed/26064978

484. Stimson RH, Walker BR: The role and regulation of 11beta-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome. Horm Mol Biol Clin Investig 2013 15:37-48.

485. Bays H, Mandarino L, DeFronzo RA: Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab 2004 89:463-478. https://www.ncbi.nlm.nih.gov/pubmed/14764748

486. Veret J, Bellini L, Giussani P, et al.: Roles of Sphingolipid Metabolism in Pancreatic beta Cell Dysfunction Induced by Lipotoxicity. J Clin Med 2014 3:646-662. https://www.ncbi.nlm.nih.gov/pubmed/26237395

487. Larsen PJ, Tennagels N: On ceramides, other sphingolipids and impaired glucose homeostasis. Mol Metab 2014 3:252-260. https://www.ncbi.nlm.nih.gov/pubmed/24749054

488. Taylor R, Al-Mrabeh A, Zhyzhneuskaya S, et al.: Remission of Human Type 2 Diabetes Requires Decrease in Liver and Pancreas Fat Content but Is Dependent upon Capacity for beta Cell Recovery. Cell Metab 2018 28:547-556 e543. https://www.ncbi.nlm.nih.gov/pubmed/30078554

489. Cefalu WT, Kaul S, Gerstein HC, et al.: Cardiovascular Outcomes Trials in Type 2 Diabetes: Where Do We Go From Here? Reflections From a Diabetes Care Editors’ Expert Forum. Diabetes Care 2018 41:14-31. https://www.ncbi.nlm.nih.gov/pubmed/29263194

490. Schnell O, Ryden L, Standl E, et al.: Updates on cardiovascular outcome trials in diabetes. Cardiovasc Diabetol 2017 16:128. https://www.ncbi.nlm.nih.gov/pubmed/29020969

491. Andrikou E, Tsioufis C, Andrikou I, et al.: GLP-1 receptor agonists and cardiovascular outcome trials: An update. Hellenic J Cardiol 2018 https://www.ncbi.nlm.nih.gov/pubmed/30528435

492. Hernandez AF, Green JB, Janmohamed S, et al.: Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 2018 392:1519-1529. https://www.ncbi.nlm.nih.gov/pubmed/30291013

493. Rosenstock J, Perkovic V, Johansen OE, et al.: Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial. JAMA 2018 https://www.ncbi.nlm.nih.gov/pubmed/30418475

494. Wiviott SD, Raz I, Bonaca MP, et al.: Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2018 https://www.ncbi.nlm.nih.gov/pubmed/30415602

495. Hsu PF, Sung SH, Cheng HM, et al.: Cardiovascular Benefits of Acarbose vs Sulfonylureas in Patients With Type 2 Diabetes Treated With Metformin. J Clin Endocrinol Metab 2018 103:3611-3619. https://www.ncbi.nlm.nih.gov/pubmed/30113697

496. Verma S, Poulter NR, Bhatt DL, et al.: Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke. Circulation 2018 138:2884-2894. https://www.ncbi.nlm.nih.gov/pubmed/30566004

497. O’Brien MJ, Karam SL, Wallia A, et al.: Association of Second-line Antidiabetic Medications With Cardiovascular Events Among Insured Adults With Type 2 Diabetes. JAMA Netw Open 2018 1:e186125.

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Obesity and High Blood Pressure

498. Landsberg L, Aronne LJ, Beilin LJ, et al.: Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment—a position paper of the The Obesity Society and The American Society of Hypertension. Obesity (Silver Spring) 2013 21:8-24. https://www.ncbi.nlm.nih.gov/pubmed/23401272

499. Kim DH, Kim C, Ding EL, et al.: Adiponectin levels and the risk of hypertension: a systematic review and meta-analysis. Hypertension 2013 62:27-32. https://www.ncbi.nlm.nih.gov/pubmed/23716587

500. Nguyen NQ, Debreceni TL, Burgstad CM, et al.: Effects of Posture and Meal Volume on Gastric Emptying, Intestinal Transit, Oral Glucose Tolerance, Blood Pressure and Gastrointestinal Symptoms After Roux-en-Y Gastric Bypass. Obes Surg 2015 25:1392-1400. https://www.ncbi.nlm.nih.gov/pubmed/25502436

501. Kawarazaki W, Fujita T: The Role of Aldosterone in Obesity-Related Hypertension. Am J Hypertens 2016 29:415-423. https://www.ncbi.nlm.nih.gov/pubmed/26927805

502. Lim K, Burke SL, Head GA: Obesity-related hypertension and the role of insulin and leptin in high-fat-fed rabbits. Hypertension 2013 61:628-634. https://www.ncbi.nlm.nih.gov/pubmed/23339171

503. Trahair LG, Horowitz M, Jones KL: Postprandial hypotension: a systematic review. J Am Med Dir Assoc 2014 15:394-409. https://www.ncbi.nlm.nih.gov/pubmed/24630686

504. Rust P, Ekmekcioglu C: Impact of Salt Intake on the Pathogenesis and Treatment of Hypertension. Adv Exp Med Biol 2017 956:61-84. https://www.ncbi.nlm.nih.gov/pubmed/27757935

505. DiNicolantonio JJ, Lucan SC: The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease. Open Heart 2014 1:e000167.

506. Barton M, Baretella O, Meyer MR: Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction. Br J Pharmacol 2012 165:591-602. https://www.ncbi.nlm.nih.gov/pubmed/21557734

507. Buckley LF, Canada JM, Del Buono MG, et al.: Low NT-proBNP levels in overweight and obese patients do not rule out a diagnosis of heart failure with preserved ejection fraction. ESC Heart Fail 2018 5:372-378. https://www.ncbi.nlm.nih.gov/pubmed/29345112

508. Engin A: Endothelial Dysfunction in Obesity. Adv Exp Med Biol 2017 960:345-379. https://www.ncbi.nlm.nih.gov/pubmed/28585207

509. Khalid U, Wruck LM, Quibrera PM, et al.: BNP and obesity in acute decompensated heart failure with preserved vs. reduced ejection fraction: The Atherosclerosis Risk in Communities Surveillance Study. Int J Cardiol 2017 233:61-66. https://www.ncbi.nlm.nih.gov/pubmed/28185703

510. Kistorp C, Bliddal H, Goetze JP, et al.: Cardiac natriuretic peptides in plasma increase after dietary induced weight loss in obesity. BMC Obes 2014 1:24. https://www.ncbi.nlm.nih.gov/pubmed/26217511 Additional references used in this section: [4][21][472][483]

Obesity and Dyslipidemia

511. Bays H, Kothari SN, Azagury DE, et al.: 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 12:468-495. https://www.ncbi.nlm.nih.gov/pubmed/27050404

512. Aguilar D, Fernandez ML: Hypercholesterolemia induces adipose dysfunction in conditions of obesity and nonobesity. Adv Nutr 2014 5:497-502. https://www.ncbi.nlm.nih.gov/pubmed/25469381

513. Collins JM, Neville MJ, Pinnick KE, et al.: De novo lipogenesis in the differentiating human adipocyte can provide all fatty acids necessary for maturation. J Lipid Res 2011 52:1683-1692. https://www.ncbi.nlm.nih.gov/pubmed/21677304

514. Chung S, Parks JS: Dietary cholesterol effects on adipose tissue inflammation. Curr Opin Lipidol 2016 27:19-25. https://www.ncbi.nlm.nih.gov/pubmed/26655292

515. Christou GA, Kiortsis DN: Adiponectin and lipoprotein metabolism. Obes Rev 2013 14:939-949. https://www.ncbi.nlm.nih.gov/pubmed/23957239

516. Ebbert JO, Jensen MD: Fat depots, free fatty acids, and dyslipidemia. Nutrients 2013 5:498-508. https://www.ncbi.nlm.nih.gov/pubmed/23434905

517. Klop B, Elte JW, Cabezas MC: Dyslipidemia in obesity: mechanisms and potential targets. Nutrients 2013 5:1218-1240. https://www.ncbi.nlm.nih.gov/pubmed/23584084

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Obesity and Non-alcoholic Fatty Liver Disease (NAFLD)

518. Choo VL, Viguiliouk E, Blanco Mejia S, et al.: Food sources of fructose-containing sugars and glycaemic control: systematic review and meta-analysis of controlled intervention studies. BMJ 2018 363:k4644. https://www.ncbi.nlm.nih.gov/pubmed/30463844

519. Jung UJ, Choi MS: Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci 2014 15:6184-6223. https://www.ncbi.nlm.nih.gov/pubmed/24733068

520. Calzadilla Bertot L, Adams LA: The Natural Course of Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2016 17

521. Kanda H, Tateya S, Tamori Y, et al.: MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 2006 116:1494-1505. https://www.ncbi.nlm.nih.gov/pubmed/16691291

522. Duwaerts CC, Maher JJ: Mechanisms of Liver Injury in Non-Alcoholic Steatohepatitis. Curr Hepatol Rep 2014 13:119-129. https://www.ncbi.nlm.nih.gov/pubmed/25045618

523. Saponaro C, Gaggini M, Carli F, et al.: The Subtle Balance between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis. Nutrients 2015 7:9453-9474. https://www.ncbi.nlm.nih.gov/pubmed/26580649

524. Barb D, Portillo-Sanchez P, Cusi K: Pharmacological management of nonalcoholic fatty liver disease. Metabolism 2016 65:1183-1195. https://www.ncbi.nlm.nih.gov/pubmed/27301803

525. Lee DH: Imaging evaluation of non-alcoholic fatty liver disease: focused on quantification. Clin Mol Hepatol 2017 23:290-301. https://www.ncbi.nlm.nih.gov/pubmed/28994271

526. Idilman IS, Keskin O, Celik A, et al.: A comparison of liver fat content as determined by magnetic resonance imaging-proton density fat fraction and MRS versus liver histology in non-alcoholic fatty liver disease. Acta Radiol 2016 57:271-278. https://www.ncbi.nlm.nih.gov/pubmed/25855666

527. Leoni S, Tovoli F, Napoli L, et al.: Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis. World J Gastroenterol 2018 24:3361-3373.

528. de Alwis NM, Anstee QM, Day CP: How to Diagnose Nonalcoholic Fatty Liver Disease. Dig Dis 2016 34 Suppl 1:19-26. https://www.ncbi.nlm.nih.gov/pubmed/27547937

529. Kneeman JM, Misdraji J, Corey KE: Secondary causes of nonalcoholic fatty liver disease. Therap Adv Gastroenterol 2012 5:199-207. https://www.ncbi.nlm.nih.gov/pubmed/22570680

530. Luukkonen PK, Sadevirta S, Zhou Y, et al.: Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars. Diabetes Care 2018 41:1732-1739. https://www.ncbi.nlm.nih.gov/pubmed/29844096

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Obesity and Cancer

532. Spyrou N, Avgerinos KI, Mantzoros CS, et al.: Classic and Novel Adipocytokines at the Intersection of Obesity and Cancer: Diagnostic and Therapeutic Strategies. Curr Obes Rep 2018 7:260-275. https://www.ncbi.nlm.nih.gov/pubmed/30145771

533. Golemis EA, Scheet P, Beck TN, et al.: Molecular mechanisms of the preventable causes of cancer in the United States. Genes Dev 2018 32:868-902. https://www.ncbi.nlm.nih.gov/pubmed/29945886

534. Druso JE, Fischbach C: Biophysical Properties of Extracellular Matrix: Linking Obesity and Cancer. Trends Cancer 2018 4:271-273. https://www.ncbi.nlm.nih.gov/pubmed/29606310

535. Islami F, Goding Sauer A, Gapstur SM, et al.: Proportion of Cancer Cases Attributable to Excess Body Weight by US State, 2011-2015. JAMA Oncol 2018 https://www.ncbi.nlm.nih.gov/pubmed/30589925

536. Sung H, Siegel RL, Torre LA, et al.: Global patterns in excess body weight and the associated cancer burden. CA Cancer J Clin 2018 https://www.ncbi.nlm.nih.gov/pubmed/30548482

537. Sung H, Siegel RL, Rosenberg PS, et al.: Emerging cancer trends among young adults in the USA: analysis of a populationbased cancer registry. Lancet Public Health 2019 https://www.ncbi.nlm.nih.gov/pubmed/30733056

538. Mackenzie H, Markar SR, Askari A, et al.: Obesity surgery and risk of cancer. Br J Surg 2018 105:1650-1657. https://www.ncbi.nlm.nih.gov/pubmed/30003539

539. Seiler A, Chen MA, Brown RL, et al.: Obesity, Dietary Factors, Nutrition, and Breast Cancer Risk. Curr Breast Cancer Rep 2018 10:14-27. 540.Liou GY, Storz P: Reactive oxygen species in cancer. Free Radic Res 2010 44:479-496.

541. Salehi B, Martorell M, Arbiser JL, et al.: Antioxidants: Positive or Negative Actors? Biomolecules 2018 8: https://www.ncbi.nlm.nih.gov/pubmed/30366441

542. Gorlach A, Dimova EY, Petry A, et al.: Reactive oxygen species, nutrition, hypoxia and diseases: Problems solved? Redox Biol 2015 6:372-385. https://www.ncbi.nlm.nih.gov/pubmed/26339717

543. Davidson KT, Zhu Z, Balabanov D, et al.: Beyond Conventional Medicine - a Look at Blueberry, a Cancer-Fighting Superfruit. Pathol Oncol Res 2018 24:733-738.

544. Turati F, Rossi M, Pelucchi C, et al.: Fruit and vegetables and cancer risk: a review of southern European studies. Br J Nutr 2015 113 Suppl 2:S102-110.

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Investigational Anti-obesity Pharmacotherapy

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547. Srivastava G, Apovian C: Future Pharmacotherapy for Obesity: New Anti-obesity Drugs on the Horizon. Curr Obes Rep 2018 7:147-161. https://www.ncbi.nlm.nih.gov/pubmed/29504049

548. Xiong Y, Walker K, Min X, et al.: Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to monkeys. Sci Transl Med 2017 9:https://www.ncbi.nlm.nih.gov/pubmed/29046435

549. Pocai A: Action and therapeutic potential of oxyntomodulin. Mol Metab 2014 3:241-251. https://www.ncbi.nlm.nih.gov/pubmed/24749050

550. Khatib MN, Gaidhane S, Gaidhane AM, et al.: Ghrelin O Acyl Transferase (GOAT) as a Novel Metabolic Regulatory Enzyme. J Clin Diagn Res 2015 9:Le01-05.

551. Zhang SR, Fan XM: Ghrelin-ghrelin O-acyltransferase system in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol 2015 21:3214-3222. https://www.ncbi.nlm.nih.gov/pubmed/25805927

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553. Liu R, Li N, Lin Y, et al.: Glucagon Like Peptide-1 Promotes Adipocyte Differentiation via the Wnt4 Mediated Sequestering of Beta-Catenin. PLoS One 2016 11:e0160212. https://www.ncbi.nlm.nih.gov/pubmed/27504979

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558. Scott R, Minnion J, Tan T, et al.: Oxyntomodulin analogue increases energy expenditure via the glucagon receptor. Peptides 2018 104:70-77. https://www.ncbi.nlm.nih.gov/pubmed/29680267

559. Persaud SJ, Bewick GA: Peptide YY: more than just an appetite regulator. Diabetologia 2014 57:1762-1769. https://www.ncbi.nlm.nih.gov/pubmed/24917132

560. Erondu N, Gantz I, Musser B, et al.: Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults. Cell Metab 2006 4:275-282. https://www.ncbi.nlm.nih.gov/pubmed/17011500

561. Erondu N, Wadden T, Gantz I, et al.: Effect of NPY5R antagonist MK-0557 on weight regain after very-low-calorie diet-induced weight loss. Obesity (Silver Spring) 2007 15:895-905. https://www.ncbi.nlm.nih.gov/pubmed/17426325

562. Camilleri M, Acosta A: Combination Therapies for Obesity. Metab Syndr Relat Disord 2018 16:390-394. https://www.ncbi.nlm.nih.gov/pubmed/29993319

563. Frias JP, Nauck MA, Van J, et al.: Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet 2018 392:2180-2193. https://www.ncbi.nlm.nih.gov/pubmed/30293770

564. Coskun T, Sloop KW, Loghin C, et al.: LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab 2018 18:3-14. https://www.ncbi.nlm.nih.gov/pubmed/30473097

565. Alexiadou K, Anyiam O, Tan T: Cracking the combination: Gut hormones for the treatment of obesity and diabetes. J Neuroendocrinol 2018 e12664. https://www.ncbi.nlm.nih.gov/pubmed/30466162

566. Bessesen DH, Van Gaal LF: Progress and challenges in anti-obesity pharmacotherapy. Lancet Diabetes Endocrinol 2018 6:237- 248.

567. Bays HE, Weinstein R, Law G, et al.: Canagliflozin: effects in overweight and obese subjects without diabetes mellitus. Obesity (Silver Spring) 2014 22:1042-1049. https://www.ncbi.nlm.nih.gov/pubmed/24227660

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