Sexual dimorphism in white and brown adipose tissue with obesity and inflammation.

This article is part of a Special Issue "Energy Balance". Obesity and its associated comorbidities remain at epidemic levels globally and show no signs of abatement in either adult or child populations. White adipose tissue has long been established as an endocrine signalling organ possessing both metabolic and immune functions. This role can become dysregulated following excess adiposity caused by adipocyte hypertrophy and hyperplasia. In contrast, brown adipose tissue (BAT) is only present in comparatively small amounts in the body but can significantly impact on heat production, and thus could prevent excess white adiposity. Obesity and associated risk factors for adverse metabolic health are not only linked with enlarged fat mass but also are dependent on its anatomical deposition. In addition, numerous studies have revealed a disparity in white adipose tissue deposition prior to and during the development of obesity between the sexes. Females therefore tend to develop a greater abundance of femoral and gluteal subcutaneous fat whereas males exhibit more central adiposity. In females, lower body subcutaneous adipose tissue depots appear to possess a greater capacity for lipid storage, enhanced lipolytic flux and hyperplastic tissue remodelling compared to visceral adipocytes. These differences are acknowledged to contribute to the poorer metabolic and inflammatory profiles observed in males. Importantly, the converse outcomes between sexes disappear after the menopause, suggesting a role for sex hormones within the onset of metabolic complications with obesity. This review further considers how BAT impacts upon on the relationship between excess adiposity, gender, inflammation and endocrine signalling and could thus ultimately be a target to prevent obesity.

Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep.

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.

The influence of sex on early stage markers of kidney dysfunction in response to juvenile obesity.

Changes within the kidney in response to obesity are critical in determining the magnitude of later dysfunction. However, the cause of this process in response to juvenile onset obesity and how it can be determined by sex is poorly understood. We therefore examined the effect of juvenile obesity induced by exposure to a restricted activity environment from weaning until early adulthood on the molecular responses within the kidney together with glomerular area and nucleated cell number. This was stratified by sex and was undertaken in a sheep model of early obesity. Despite a similar magnitude of increase in fat mass with obesity onset between sexes, adverse effects on glomerular area and cell number together with raised gene expression within the kidney only occurred in males. Irrespective of obesity, gene expression of C-C motif receptor 2 was higher, and interleukin-6 lower, in male kidneys compared with female kidneys. The effects of sex on molecular differences within the kidney were amplified with obesity, which had no effect on any gene studied in females but had an enhanced response in males. Obese males therefore showed increased gene expression of a range of markers relating to the glucocorticoid axis, inflammation, and lipid sensing. In conclusion, young females were protected from adverse renal effects of obesity, which results in very little inflammatory or related responses. Our findings emphasize the critical importance of sex specificity in disease pathogenesis. An increased understanding of the specific mechanisms will have important implications for therapeutic strategies aimed at preventing adverse consequences of obesity.