Sex Differences in Metabolic and Adipose Tissue Responses to Juvenile-Onset Obesity in Sheep

Abstract

Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissue depots. Despite a similar increase in fat mass with obesity between genders, males demonstrated a higher storage capacity of lipids within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast, obese females became hypercortisolemic, a response that was positively correlated with central fat mass. Analysis of gene expression in perirenal-abdominal adipose tissue demonstrated the stimulation of inflammatory markers in males, but not females, with obesity. Obese females displayed increased expression of genes involved in the glucocorticoid axis and energy sensing in perirenal-abdominal, but not omental, adipose tissue, indicating a depot-specific mechanism that may be protective from the adverse effects of metabolic dysfunction and inflammation. In conclusion, young males are at a greater risk than females to the onset of comorbidities associated with juvenile-onset obesity. These sex-specific differences in cortisol and adipose tissue could explain the earlier onset of the metabolic-related diseases in males compared with females after obesity.

Early adipose deposits in sheep: comparative analysis of the perirenal fat transcriptome of Assaf and Churra suckling lambs

“…; Bloor et al . ). This work could support the value of the lamb as an appropriate model to assess the influence of different factors (e.g.…”

Fat mass- and obesity-associated gene Fto affects the dietary response in mouse white adipose tissue

“…In fact, the capacity of white adipocytes to become hypertrophic in response to obesity is a key factor in the pathogenicity of excessive weight gain 18 . The size of the white adipocyte is highly correlated with its capacity to become insulin resistant 19 and also associated with the pro-inflammatory activity of the white adipose tissue as a result of various mechanisms including the endoplasmic reticulum stress response 20 . In the current study, the fat and lean mass was not quantified separately hence the number of adipocytes cannot be directly examined.…”

An evolving scientific basis for the prevention and treatment of pediatric obesity

“…62 Neither examining methylation profiles in blood nor looking at fractional changes in methylation of a gene provides many insights into obesity and related disease processes. 63,64 It is also apparent that the impact of pediatric obesity is strongly influenced by gender, 65 with evidence that females are apparently being protected from the adverse effects of excess adiposity on a range of metabolic processes including inflammatory responses within the kidney. 66 …”