Resistance to Aging‐Associated Obesity in Capsaicin‐Desensitized Rats One Year after Treatment

Abstract

Resistance to aging-associated obesity in capsaicindesensitized rats one year after treatment. Obes Res.Previous studies demonstrated reduced weight of abdominal white adipose tissue depots and of carcass fat in capsaicin-desensitized (Cap-Des) rats up to 8 months after treatment. The objective of the present study was to find out whether aging-associated obesity and hyperplasia of retroperitoneal white adipose tissue was prevented in older (13.5 month old) CapDes rats, one year after treatment with Cap (done when they were 1.5 months old). The prevalence of obesity is known to increase in rats by this age. Abdominal white adipose tissue depots weighed less in old Cap-Des rats, both epididymal (9% less) and retroperitoneal (30% less). The number of mature white adipocytes was 28% less in the retroperitoneal depot but was not significantly different in the epididymal depot. Adipocyte size was not different. Carcass fat was less, both total and as percent of body weight. Food intake was normal for their reduced body size. The exponential increase in retroperitoneal white adipose tissue weight characteristic of aging rats that are becoming obese was virtually absent in Cap-Des rats. We conclude that lack of function of capsaicin-sensitive afferent autonomic nerves, known to be destroyed in Cap-Des rats, results in an alteration in energy balance conducive to leanness. We suggest that the attenuated MELNYK, ANNA AND JEAN HIMMS-HAGEN. age-associated increase in circulating CGRP (derived mainly from capsaicin-sensitive nerves) in the CapDes rat results in a lower degree of aging-associated insulin-resistance, hence in a lesser degree of obesity.

Neonatal capsaicin causes compensatory adjustments to energy homeostasis in rats

“…However, CAP-treated rats have similar daily food intake [7], similar or even lower body weight [8] and improved glucose homeostatic control [17] compared to controls. Furthermore, deafferentated animals have a long-term decrease in white adipose tissue mass [9] and are more resistant to ageing-associated obesity [10]. Finally, CAP treatment results in increased whole body insulin sensitivity [11] and a lower degree of ageing-associated insulin resistance [10].…”

“…Furthermore, deafferentated animals have a long-term decrease in white adipose tissue mass [9] and are more resistant to ageing-associated obesity [10]. Finally, CAP treatment results in increased whole body insulin sensitivity [11] and a lower degree of ageing-associated insulin resistance [10]. These observations indicate that CAP-treated animals are able, or even have improved capability, to maintain body weight and energy homeostasis, despite the fact that they lack seemingly important information transmitted via vagal afferents to the CNS.…”

Treating Diet-Induced Obesity: A New Role for Vagal Afferents?

“…One way to overcome the adverse side effects of vagotomy and retain some of the benefits was to reduce or avoid damage to the vagal pre-motor axons. Indeed, selective sensory vagotomy may retain some of the benefits as it reduces food intake, body weight, and fat accumulation in rodent obesity models [6,7]. Moreover, sensory vagotomy reduced the excess abdominal visceral fat found in aging rats [7].…”

“…Indeed, selective sensory vagotomy may retain some of the benefits as it reduces food intake, body weight, and fat accumulation in rodent obesity models [6,7]. Moreover, sensory vagotomy reduced the excess abdominal visceral fat found in aging rats [7]. Stearns et al [8] took this approach further by distinguishing the effects of sensory vagotomy on different fat depots in rats subjected to diet-induced obesity (DIO).…”

“…Groups that receive no treatment, sham surgery or vagotomy and are fed normal energy-diet provide baselines that permit one to distinguish, for example, the actual degree of obesity in each group, rather than just the relative degree. Also, the proportions of the obesity and excess visceral fat due to aging [7] versus diet [8] could be distinguished, both with and without vagotomy. Further, since capsaicin only partially reduces the number of vagal GI afferents, it might be useful to assess residual vagal function, e.g.…”