Sexually dimorphic responses to fat loss after caloric restriction or surgical lipectomy

Abstract

Specifically, males tend to accumulate relatively more visceral fat, whereas females accumulate relatively more subcutaneous fat. The phenomenon of maintaining typical sex-specific fat distributions suggests sex-specific mechanisms that regulate energy balance and adiposity. We used two distinct approaches to reduce fat mass, caloric restriction (CR), and surgical fat removal (termed lipectomy) and assessed parameters involved in the regulation of energy balance. We found that male and female mice responded differentially to CR-and to lipectomy-induced fat loss. Females decreased energy expenditure during CR or after lipectomy. In contrast, males responded by eating more food during food return after CR or after lipectomy. Female CR mice conserved subcutaneous fat, whereas male CR mice lost adiposity equally in the subcutaneous and visceral depots. In addition, female mice had a reduced capability to restore visceral fat after fat loss. After CR, plasma leptin levels decreased in male but not in female mice. The failure to increase food intake after returning to ad libitum intake in females could be due to the relatively stable levels of leptin. In summary, we have found sexual dimorphisms in the response to fat loss that point to important underlying differences in the strategies by which male and female mice regulate body weight. food intake; energy expenditure; leptin; subcutaneous fat; visceral fat THE WORLDWIDE PREVALENCE OF obesity with its accompanying comorbidities, including type 2 diabetes, cardiovascular disease, and cancer (7,41,58), continues to rise and has reached epidemic proportions (22,59,81). White adipose tissue (WAT) is the principal site for lipid accumulation in the body, and decreasing WAT is an important therapeutic goal because it would reduce medical complications. This is difficult to achieve, however, because total body fat is regulated by a robust and accurate process that matches energy intake to energy expenditure over time (39). Demonstrations of this include the failure of humans to maintain weight and fat loss after dieting (24, 75) and liposuction surgeries (6) and the return to baseline fat levels after caloric restriction (CR) or partial lipectomy in rodent models.CR and lipectomy represent two ways to accomplish decreased adiposity. CR leads to a spectrum of changes, including decreased basal metabolic rate (33), increased spontaneous activity (32, 56, 65), increased lipid mobilization (26, 37), and many others that collectively lead to reduced body fat (60). In contrast, surgical removal of fat via lipectomy may result in comparably decreased body fat, but the fat loss is specific to selected fat depots depending on the removal site. Altered metabolism and behavior after lipectomy induce compensatory enlargement of nonexcised WAT pads in many species, including mice and rats (48). The fat restoration after either CR or lipectomy is consistent with the hypothesis that total body fat is highly defended and maintained.In humans, the distribution of body fat differs between ma...

Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restriction☆

“…The discrepancy between previous and present findings may be explained by the sex of the mice used in each study. Evidence suggests that white adipose tissue in female mice responds differently to dietary restriction regimens, when compared to that of male mice [22]. Female mice conserve subcutaneous fat during periods of CR, while male CR mice lose adiposity equally in the subcutaneous and visceral depots [22].…”

“…Evidence suggests that white adipose tissue in female mice responds differently to dietary restriction regimens, when compared to that of male mice [22]. Female mice conserve subcutaneous fat during periods of CR, while male CR mice lose adiposity equally in the subcutaneous and visceral depots [22]. Moreover, female mice exhibit a reduced capability to restore visceral fat during periods of CR [22].…”

Pathophysiology of Human Visceral Obesity: An Update

“…In men, low circulating levels of total testosterone are generally associated with abdominal and/or visceral obesity (178, 431,497,507). Whether free testosterone levels are related to body fat distribution patterns remains uncertain due to methodological limitations in the measurement of free testosterone (470,595).…”

“…Whether free testosterone levels are related to body fat distribution patterns remains uncertain due to methodological limitations in the measurement of free testosterone (470,595). Some investigators have reported low free testosterone in viscerally obese men (507). Many studies also demonstrated that plasma concentrations of sex hormone-binding globulin (SHBG), a determinant of testosterone bioavailability, are negatively associated with abdominal obesity in both men and women (90,178,180,257,497,431,552,572).…”

Calorie restriction and susceptibility to intact pathogens

“…Because so much is known about the effects of CR on laboratory rodents, they would initially be a useful host to use for research with intact pathogens. Of course, there is variation in response to CR even among inbred mouse strains (Turturro et al 1999;Brochmann et al 2003;Rikke et al 2003Rikke et al , 2006, as well as between males and females (Wu et al 2003a;Shi et al 2007). Mouse strain and sex also influence susceptibility to pathogens (Zuk and McKean 1996;Morales-Montor et al 2004;, and these effects are pathogen-specific.…”