Sex and Species Differences in the Development of Diet-Induced Obesity and Metabolic Disturbances in Rodents

Abstract

Prevalence and health consequences of obesity differ between men and women. Yet, most preclinical studies investigating the etiology of obesity have, to date, been conducted in male rodents. Notably, diet is a major determinant of obesity, but sex differences in rodent models of diet-induced obesity, and the mechanisms that underlie such differences, are still understudied. Here, we aim to determine whether time course and characteristics of diet-induced obesity differ between sexes in rats and mice, and to investigate the potential causes of the observed divergence. To achieve this, we offered the most commonly tested rodents of both sexes, SD rats and C57BL/6 mice, a free choice of 60 % high-fat diet (HFD) and regular chow; body weight, food intake, fat mass, brown adipose responses, locomotor activity and glucose tolerance were assessed in a similar manner in both species. Our results indicate that overall diet-induced hyperphagia is greater in males but that females display a higher preference for the HFD, irrespective of species. Female rats, compared to males, showed a delay in diet-induced weight gain and less metabolic complications. Although male rats increased brown adipose tissue thermogenesis in response to the HFD challenge, this was not sufficient to counteract increased adiposity. In contrast to rats, female and male mice presented with a dramatic adiposity and impaired glucose tolerance, and a decreased energy expenditure. Female mice showed a 5-fold increase in visceral fat, compared to 2-fold increase seen in male mice. Overall, we found that male and female rodents responded very differently to HFD challenge, and engaged different compensatory energy expenditure mechanisms. In addition, these sex differences are divergent in rats and mice. We conclude that SD rats have a better face validity for the lower prevalence of overweight in women, while C57BL/6 mice may better model the increased prevalence of morbid obesity in women.

Glucagon-like peptide-1 receptors in the gustatory cortex influence food intake

“…To accomplish this, C57BL/6J mice were given ad libitum access to either low fat (LF; 10% kcal fat) or high fat diet (HD; 60% kcal fat) for 6 weeks to induce diet-induced obesity (DIO) or not in the HD or LD groups, respectively. Consistent with prior reports, we observed an increase in body weight in HF-maintained animals soon upon diet onset (e.g., (Williams et al, 2011; Honors et al, 2012; Salinero et al, 2018; Maric et al, 2022)). There was a significant main effect of diet, time on diet, and an interaction between diet x time on change in body weight (two-way ANOVA, diet: F(1,33)=30.06, p<0.0001; time: F(1.751,57.80)=66.73, p<0.0001; interaction: F(5,165)=26.99, p<0.0001; Fig 5A ).…”

“…To accomplish this, C57BL/6J mice were given ad libitum access to either low fat (LF; 10% kcal fat) or high fat diet (HD; 60% kcal fat) for 6 weeks to induce diet-induced obesity (DIO) or not in the HD or LD groups, respectively. Consistent with prior reports, we observed an increase in body weight in HF-maintained animals soon upon diet onset (e.g., (Williams et al, 2011;Honors et al, 2012;Salinero et al, 2018;Maric et al, 2022)). There was a significant (Hwang et al, 2010;Carlin et al, 2016;Salinero et al, 2018;Maric et al, 2022), we observed a robust sex-difference in DIO expression, wherein females exhibited less weight gain as compared to males when maintained on the same HF diet…”

“…Consistent with prior reports, we observed an increase in body weight in HF-maintained animals soon upon diet onset (e.g., (Williams et al, 2011;Honors et al, 2012;Salinero et al, 2018;Maric et al, 2022)). There was a significant (Hwang et al, 2010;Carlin et al, 2016;Salinero et al, 2018;Maric et al, 2022), we observed a robust sex-difference in DIO expression, wherein females exhibited less weight gain as compared to males when maintained on the same HF diet…”

Repetitive transcranial direct current stimulation modulates the brain–gut–microbiome axis in obese rodents

“…In the present study, we have shown that both HCD and AtDCS can affect feeding behavior, metabolic parameters as well as main phyla of the gut microbiota of female Wistar rats. Because sex and species differences in the development of diet-induced obesity and metabolic disturbances in rodents were described [70], we aimed at investigating if our feeding and stimulation protocols [50,51,69] were effective regardless of gender. It was shown [70] that diet-induced hyperphagia is greater in males offered a high-fat diet, irrespective of species, and female rats show a delay in diet-induced obesity and metabolic complications due to higher energy expenditure and lower level of hyperphagia.…”

“…Because sex and species differences in the development of diet-induced obesity and metabolic disturbances in rodents were described [70], we aimed at investigating if our feeding and stimulation protocols [50,51,69] were effective regardless of gender. It was shown [70] that diet-induced hyperphagia is greater in males offered a high-fat diet, irrespective of species, and female rats show a delay in diet-induced obesity and metabolic complications due to higher energy expenditure and lower level of hyperphagia. Furthermore, obese female and male rodents obtained a dramatic adiposity and glucose intolerance, probably due to a decreased energy expenditure and to higher intake of saturated fats compared to the lean controls.…”