Higher White Adipocyte Area and Lower Leptin Production in Adult Rats Overfed During Lactation

Abstract

Litter size reduction during lactation is a good model for childhood obesity since it induces overnutrition and programming for obesity at adulthood. Adult offspring develop higher fat mass content, hyperinsulinemia and insulin resistance, hypertension, lower HDL cholesterol, hyperphagia, and leptin resistance. Leptin resistance is often associated with hyperleptinemia. Although we observed higher SOCS3 and lower STAT3 in the hypothalamus of rats raised in small litters featuring a central leptin resistance, they showed unexpected normoleptinemia at 180 days old. Then, to clarify why early overfed rats did not develop hyperleptinemia when adult, we studied the leptin production by the visceral and subcutaneous adipose tissue and skeletal muscle as well as the morphology in the 2 different fat depots. To induce EO, litter size was reduced to 3 pups/litter (SL group) on the 3^rd day of life. In controls (NL group), litter size was adjusted to 10 pups/litter. Rats were killed at 180 days old. The programming of adipose tissue morphology by early overnutrition is specific between the different fat depots with hypertrophy only in the visceral compartment. In addition, the visceral adipocyte showed lower leptin content that may indicate a reduced leptin synthesis. These data suggest that adipocytes from SL rats are dysfunctional, since a higher leptin production in larger adipose cells is expected. In conclusion, postnatal nutrition is determinant for future leptin production by different fat depots as well as adipocyte morphology. These changes seem to be related to the severity of obesity and its metabolic consequences.

References

• 1 Ahima RS, Osei SY. Front Horm Res. 2008;  36 182-197
• 2 Burdge GC, Hanson MA, Slater-Jefferies JL, Lillycrop KA. Br J Nutr. 2007;  97 1036-1046
• 3 de Moura EG, Lisboa PC, Passos MC. Neuroimmunomodulation. 2008;  15 176-188
• 4 Plagemann A, Heidrich I, Gotz F, Rohde W, Dorner G. Exp Clin Endocrinol. 1992;  99 154-158
• 5 Velkoska E, Cole TJ, Morris MJ. Am J Physiol Endocrinol Metab. 2005;  288 E1236-E1243
• 6 Rodrigues AL, de Moura EG, Passos MC, Potente Dutra SC, Lisboa PC. J Physiol. 2009;  587 2647-2661
• 7 Rodrigues AL, de Moura EG, Passos MC, Trevenzoli IH, Conceição EPS, Bonono II, Neto JFN, Lisboa PC. J Nutr Biochem. 2011;  22 109-117
• 8 Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens ZW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF. N Engl J Med. 1996;  334 292-295
• 9 Trevenzoli IH, Rodrigues AL, Oliveira E, Thole AA, Carvalho L, Figueiredo MS, Toste FP, Neto JFN, Passos MCF, Lisboa PC, Moura EG. Horm Metab Res. 2010;  42 483-490
• 10 Paz-Filho GJ, Volaco A, Suplicy HL, Radominski RB, Boguszewski CL. Arq Bras Endocrinol Metabol. 2009;  53 1088-1095
• 11 Bjorbaek C, Kahn BB. Recent Prog Horm Res. 2004;  59 305-331

Correspondence