Early Overfeed-Induced Obesity Leads to Brown Adipose Tissue Hypoactivity in Rats

Abstract

Background/Aims: Brown adipose tissue activation has been considered a potential anti-obesity mechanism because it is able to expend energy through thermogenesis. In contrast, white adipose tissue stores energy, contributing to obesity. We investigated whether the early programming of obesity by overfeeding during lactation changes structure of interscapular brown adipose tissue in adulthood and its effects on thermogenesis. Methods: Birth of litters was considered day 0. On day 2, litter size was adjusted to normal (9 pups) and small (3 pups) litters. On day 21, the litters were weaned. A temperature transponder was implanted underneath interscapular brown adipose tissue pads of 81-day-old animals; local temperature was measured during light and dark periods between days 87 and 90. The animals were euthanized, and tissue and blood samples were collected for further analysis. The vagus and retroperitoneal sympathetic nerve activity was recorded. Results: Small litter rats presented significant lower interscapular brown adipose tissue temperature during the light (NL 37.6°C vs. SL 37.2°C) and dark (NL 38°C vs. SL 37.6°C) periods compared to controls. Morphology of small litter brown adipose tissue showed fewer lipid droplets in the tissue center and more and larger in the periphery. The activity of vagus nerve was 19,9% greater in the small litter than in control (p<0.01), and no difference was observed in the sympathetic nerve activity. In adulthood, the small litter rats were 11,7% heavier than the controls and presented higher glycemia 13,1%, insulinemia 70% and corticosteronemia 92,6%. Conclusion: Early overfeeding programming of obesity changes the interscapular brown adipose tissue structure in adulthood, leading to local thermogenesis hypoactivity, which may contribute to obesity in adults.

Newborn feeding recommendations and practices increase the risk of development of overweight and obesity

“…In rodent studies, overfeeding as early as the second day of life has been shown to lead to brown adipose tissue hypo-activity. This supports the early programming hypothesis for obesity risk, as brown adipose tissue is protective against obesity through energy expenditure needed for thermogenesis [8]. Additionally, early overfeeding in female rats has been shown to have long-term dysregulatory effects in the ghrelin signaling pathway [9].…”

Adipose tissue uncoupling protein 1 levels and function are increased in a mouse model of developmental obesity induced by maternal exposure to high-fat diet

“…41 Overfeeding rodents in the first few weeks of life have resulted in lower levels of UCP1 and changes in BAT structure in adulthood. 42,43 Supplementation of obese ewes with Larginine has led to a significant increase in fetal BAT, among other metabolic improvements, while maternal diet supplementation with olive oil, protein or fiber has increased UCP1 expression in the BAT of rat pups. 40,44,45 Only one of these studies reported gender differences in UCP1 expression.…”

Maternal high-fat diet during lactation impairs thermogenic function of brown adipose tissue in offspring mice

“…There is concrete evidence supporting the association between maternal obesity and high energy intake with obesity and metabolic dysfunction in offspring 1 2 . Feeding the dam with high-fat diet (HFD) is the most common method to induce maternal obesity and over-nutrition in rodents 3 4 5 6 . Previous studies have demonstrated that lactation HFD predisposes offspring to obesity and metabolic disorder in rats 5 , and severely affects offspring metabolic profiles and neural development 4 .…”