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Obesity research in the next decade

Abstract

The obesity epidemic demands more insight into genetic predisposition, mechanisms, prevention and therapeutic interventions. Opinions about how to prioritize obesity research in the next decade are many and highly varied. However, in this article I have chosen three areas of focus that arguably should be at the top of the list. These include: (1) the physiologic basis of body weight and body fat regulation; (2) epigenetic mechanisms of energy balance; and (3) the prevention of obesity. The approach needs to be translational and bi-directional with a strong emphasis on basic science including studies of relevant gene expression and animal models of energy balance. Clinical research into mechanisms can challenge the existing paradigms that could direct research back to more basic understanding or to applications to populations at risk. Communication between scientists and physicians at the far end of the spectrum needs new and ongoing emphasis.

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References

  1. Wolfe RR, Volpi E . Insulin and protein metabolism. In: Jefferson LS, Cherrington AD (eds). Handbook of Physiology. Oxford: New York, 2001, pp 735–757.

    Google Scholar 

  2. Owen OE, Smalley KJ, D’Alessio DA, Mozzoli MA, Dawson EK . Protein, fat, and carbohydrate requirements during starvation: anaplerosis and cataplerosis. Am J Clin Nutr 1998; 68: 12–34.

    Article  CAS  PubMed  Google Scholar 

  3. Cherel Y, Robin JP, Heitz A, Calgari C, Le Maho Y . Relationships between lipid availability and protein utilization during prolonged fasting. J Comp Physiol [B] 1992; 162: 305–313.

    Article  CAS  Google Scholar 

  4. Neel JV . Diabetes mellitus: a ‘thrifty’ genotype rendered detrimental by ‘progress’? Am J Hum Genet 1962; 14: 353–362.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Speakman JR . A nonadaptive scenario explaining the genetic predisposition to obesity: the ‘predation release’ hypothesis. Cell Metab 2007; 6: 5–12.

    Article  CAS  PubMed  Google Scholar 

  6. Veldhuis JD, Roemmich JN, Richmond EJ, Rogol AD, Lovejoy JC, Sheffield-Moore M et al. Endocrine control of body composition in infancy, childhood, and puberty. Endocr Rev 2005; 26: 114–146.

    Article  CAS  PubMed  Google Scholar 

  7. Kaplowitz PB . Link between body fat and the timing of puberty. Pediatrics 2008; 121 (Suppl 3): S208–S217.

    Article  PubMed  Google Scholar 

  8. Frisch RE, Revelle R . Height and weight at menarche and a hypothesis of menarche. Arch Dis Child 1971; 46: 695–701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kaplowitz PB . Link between body fat and the timing of puberty. Pediatrics 2008; 121 (Suppl 3): S208–S217.

    Article  PubMed  Google Scholar 

  10. Kennedy GC . The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond B Biol Sci 1953; 140: 578–596.

    Article  CAS  PubMed  Google Scholar 

  11. Speakman JR, Stubbs RJ, Mercer JG . Does body mass play a role in the regulation of food intake? Proc Nutr Soc 2002; 61: 473–487.

    Article  PubMed  Google Scholar 

  12. Berthoud HR . Interactions between the ‘cognitive’ and ‘metabolic’ brain in the control of food intake. Physiol Behav 2007; 91: 486–498.

    Article  CAS  PubMed  Google Scholar 

  13. Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med 2002; 346: 570–578.

    Article  CAS  PubMed  Google Scholar 

  14. Wadden TA, Phelan S . Behavioral assessment of the obese patient. In: Wadden TA, Stunkard AJ (eds). Handbook of Obesity Treatment. Guilford Press: New York, 2002, pp 186–226.

    Google Scholar 

  15. Rosenbaum M, Goldsmith R, Bloomfield D, Magnano A, Weimer L, Heymsfield S et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest 2005; 115: 3579–3586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bouchard C, Tremblay A, Despres JP, Nadeau A, Lupien PJ, Moorjani S et al. Overfeeding in identical twins: 5-year post-overfeeding results. Metabolism 1996; 45: 1042–1050.

    Article  CAS  PubMed  Google Scholar 

  17. Eckel RH . Non-surgical treatment of obesity. N Engl J Med 2008; 1: 1941–1950.

    Article  Google Scholar 

  18. Wadden TA, Considine RV, Foster GD, Anderson DA, Sarwer DB, Caro JS . Short- and long-term changes in serum leptin dieting obese women: effects of caloric restriction and weight loss. J Clin Endocrinol Metab 1998; 83: 214–218.

    CAS  PubMed  Google Scholar 

  19. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002; 346: 1623–1630.

    Article  PubMed  Google Scholar 

  20. de Luis DA, Gonzalez SM, Conde R, Aller R, Izaola O . Decreased basal levels of glucagon-like peptide-1 after weight loss in obese subjects. Ann Nutr Metab 2007; 51: 134–138.

    Article  CAS  PubMed  Google Scholar 

  21. Doucet E, Imbeault P, St Pierre S, Almeras N, Mauriege P, Richard D et al. Appetite after weight loss by energy restriction and a low-fat diet-exercise follow-up. Int J Obes Relat Metab Disord 2000; 24: 906–914.

    Article  CAS  PubMed  Google Scholar 

  22. Drewnowski A, Holden-Wiltse J . Taste responses and food preferences in obese women: effects of weight cycling. Int J Obes Relat Metab Disord 1992; 16: 639–648.

    CAS  PubMed  Google Scholar 

  23. Friedman JE, Dohm GL, Leggett-Frazier N, Elton CW, Tapscott EB, Pories WP et al. Restoration of insulin responsiveness in skeletal muscle of morbidly obese patients after weight loss. Effect on muscle glucose transport and glucose transporter GLUT4. J Clin Invest 1992; 89: 701–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Henry RR, Wiest-Kent TA, Scheaffer L, Kolterman OG, Olefsky JM . Metabolic consequences of very-low-calorie diet therapy in obese non-insulin-dependent diabetic and nondiabetic subjects. Diabetes 1986; 35: 155–164.

    Article  CAS  PubMed  Google Scholar 

  25. Olefsky J, Reaven GM, Farquhar JW . Effects of weight reduction on obesity. Studies of lipid and carbohydrate metabolism in normal and hyperlipoproteinemic subjects. J Clin Invest 1974; 53: 64–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Eckel RH, Yost TJ, Jensen DR . Sustained weight reduction in moderately obese women results in decreased activity of skeletal muscle lipoprotein lipase. Eur J Clin Invest 1995; 25: 396–402.

    Article  CAS  PubMed  Google Scholar 

  27. Eckel RH, Yost TJ . Weight reduction increases adipose tissue lipoprotein lipase responsiveness in obese women. J Clin Invest 1987; 80: 992–997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kelley DE, Goodpaster B, Wing RR, Simoneau JA . Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol 1999; 277 (Part 1): E1130–E1141.

    CAS  PubMed  Google Scholar 

  29. Froidevaux F, Schutz Y, Christin L, Jequier E . Energy expenditure in obese women before and during weight loss, after refeeding, and in the weight-relapse period. Am J Clin Nutr 1993; 57: 35–42.

    Article  CAS  PubMed  Google Scholar 

  30. Sandoval D, Cota D, Seeley RJ . The integrative role of CNS fuel-sensing mechanisms in energy balance and glucose regulation. Annu Rev Physiol 2008; 70: 513–535.

    Article  CAS  PubMed  Google Scholar 

  31. Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Arnold ME, Steinberg CM . Effects of sibutramine plus orlistat in obese women following 1 year of treatment by sibutramine alone: a placebo-controlled trial. Obes Res 2000; 8: 431–437.

    Article  CAS  PubMed  Google Scholar 

  32. Feinberg AP . Epigenetics at the epicenter of modern medicine. JAMA 2008; 299: 1345–1350.

    Article  CAS  PubMed  Google Scholar 

  33. Feinberg AP, Vogelstein B . Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 1983; 301: 89–92.

    Article  CAS  PubMed  Google Scholar 

  34. Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring) 2006; 14: 529–644.

    Article  Google Scholar 

  35. Kopelman PG . Obesity as a medical problem. Nature 2000; 404: 635–643.

    Article  CAS  PubMed  Google Scholar 

  36. Dong C, Li WD, Geller F, Lei L, Li D, Gorlova OY et al. Possible genomic imprinting of three human obesity-related genetic loci. Am J Hum Genet 2005; 76: 427–437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ravelli AC, Der Meulen JH, Osmond C, Barker DJ, Bleker OP . Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 1999; 70: 811–816.

    Article  CAS  PubMed  Google Scholar 

  38. Singhal A, Lucas A . Early origins of cardiovascular disease: is there a unifying hypothesis? Lancet 2004; 363: 1642–1645.

    Article  PubMed  Google Scholar 

  39. Symonds ME, Pearce S, Bispham J, Gardner DS, Stephenson T . Timing of nutrient restriction and programming of fetal adipose tissue development. Proc Nutr Soc 2004; 63: 397–403.

    Article  PubMed  Google Scholar 

  40. Zambrano E, Bautista CJ, Deas M, Martinez-Samayoa PM, Gonzalez-Zamorano M, Ledesma H et al. A low maternal protein diet during pregnancy and lactation has sex- and window of exposure-specific effects on offspring growth and food intake, glucose metabolism and serum leptin in the rat. J Physiol 2006; 571 Part 1: 221–230.

    Article  CAS  PubMed  Google Scholar 

  41. Junien C, Nathanielsz P . Report on the IASO Stock Conference 2006: early and lifelong environmental epigenomic programming of metabolic syndrome, obesity and type II diabetes. Obes Rev 2007; 8: 487–502.

    Article  CAS  PubMed  Google Scholar 

  42. Vickers MH, Gluckman PD, Coveny AH, Hofman PL, Cutfield WS, Gertler A et al. Neonatal leptin treatment reverses developmental programming. Endocrinology 2005; 146: 4211–4216.

    Article  CAS  PubMed  Google Scholar 

  43. Bouret SG, Draper SJ, Simerly RB . Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 2004; 304: 108–110.

    Article  CAS  PubMed  Google Scholar 

  44. Bogdarino I, Welham S, King PJ, Burns SP, Clark AJ . Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. Circ Res 2007; 100: 520–526.

    Article  Google Scholar 

  45. Walley AJ, Blakemore AI, Froguel P . Genetics of obesity and the prediction of risk for health. Hum Mol Genet 2006; 15 Spec No 2: R124–R130.

    Article  CAS  PubMed  Google Scholar 

  46. Ford ES, Ajani UA, Croft JB, Critchley JA, Labarthe DR, Kottke TE et al. Explaining the decrease in US deaths from coronary disease 1980–2000. N Engl J Med 2007; 356/23: 2388–2398.

    Article  Google Scholar 

  47. Finkelstein EA, Fiebelkorn IC, Wang G . National medical spending attributable to overweight and obesity: how much, and who's paying? Health Aff (Millwood) 2003; Suppl Web Exclusives: W3–W26.

  48. http://www.prwebdirect.com/releases/2007/4/prweb520127.php.

  49. Singhal A, Lucas A . Early origins of cardiovascular disease: is there a unifying hypothesis? Lancet 2004; 363: 1642–1645.

    Article  PubMed  Google Scholar 

  50. Ravelli AC, Der Meulen JH, Osmond C, Barker DJ, Bleker OP . Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 1999; 70: 811–816.

    Article  CAS  PubMed  Google Scholar 

  51. Vause T, Martz P, Richard F, Gramlich L . Nutrition for healthy pregnancy outcomes. Appl Physiol Nutr Metab 2006; 31: 12–20.

    Article  CAS  PubMed  Google Scholar 

  52. Hillier TA, Pedula KL, Schmidt MM, Mullen JA, Charles MA, Pettitt DJ . Childhood obesity and metabolic imprinting: the ongoing effects of maternal hyperglycemia. Diabetes Care 2007; 30: 2287–2292.

    Article  PubMed  Google Scholar 

  53. Jovanovic L, Nakai Y . Successful pregnancy in women with type 1 diabetes: from preconception through postpartum care. Endocrinol Metab Clin North Am 2006; 35: 79–97, vi.

    Article  PubMed  Google Scholar 

  54. Kranz S, Findeis JL, Shrestha SS . Use of the Revised Children's Diet Quality Index to assess preschooler's diet quality, its sociodemographic predictors, and its association with body weight status. J Pediatr (Rio J) 2008; 84: 26–34.

    Article  Google Scholar 

  55. Kropski JA, Keckley PH, Jensen GL . School-based obesity prevention programs: an evidence-based review. Obesity (Silver Spring) 2008; 16: 1009–1018.

    Article  Google Scholar 

  56. Barlow SE . Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics 2007; 120 (Suppl 4): S164–S192.

    Article  PubMed  Google Scholar 

  57. Kuczmarski RJ, Flegal KM, Campbell SM, Johnson CL . Increasing prevalence of overweight among US adults. The National Health and Nutrition Examination Surveys, 1960 to 1991. JAMA 1994; 272: 205–211.

    Article  CAS  PubMed  Google Scholar 

  58. Kahn HS, Cheng YJ . Longitudinal changes in BMI and in an index estimating excess lipids among white and black adults in the United States. Int J Obes (London) 2008; 32/1: 136–143.

    Article  Google Scholar 

  59. Goel MS, McCarthy EP, Phillips RS, Wee CC . Obesity among US immigrant subgroups by duration of residence. JAMA 2004; 292: 2860–2867.

    Article  CAS  PubMed  Google Scholar 

  60. Baumgartner RN . Body composition in healthy aging. Ann N Y Acad Sci 2000; 904: 437–448.

    Article  CAS  PubMed  Google Scholar 

  61. Janssen I, Ross R . Linking age-related changes in skeletal muscle mass and composition with metabolism and disease. J Nutr Health Aging 2005; 9/6: 408–419.

    Google Scholar 

  62. Zamboni M, Mazzali G, Zoico E, Harris TB, Meigs JB, Di Francesco V et al. Health consequences of obesity in the elderly: a review of four unresolved questions. Int J Obes (London) 2005; 29: 1011–1029.

    Article  CAS  Google Scholar 

  63. http://www.healthiergeneration.org/.

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Correspondence to R H Eckel.

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Robert H Eckel has received consulting fees from Sanofi Aventis, lecture fees from Sanofi Aventis, Merck, Medicor Learning, Committee of Cardiovascular and Metabolic Diseases, and the Cardiometabolic Health Congress. In addition Robert H Eckel has received grant support from the American Diabetes Association.

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Eckel, R. Obesity research in the next decade. Int J Obes 32 (Suppl 7), S143–S151 (2008). https://doi.org/10.1038/ijo.2008.251

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