ReviewSexual dimorphism in white and brown adipose tissue with obesity and inflammation
Section snippets
Overview
Current body mass index (BMI), which is used to define obesity, suggests that over 30% of all male and females irrespective of age are obese in the USA (CDC, 2013). This incidence has now started to stabilise in this adult population, in association with enhanced public awareness (Flegal et al., 2012, Ogden et al., 2012). However, a worrying statistic in children shows that although obesity rates have plateaued in girls, for boys the prevalence continues to rise (CDC, 2013). These trends are
White adipose tissue
White adipose tissue (WAT) is categorized as a loose connective tissue with a highly organised vasculature and has a range of functions in addition to structural cushioning, passive insulation and lipid storage (Trayhurn and Beattie, 2001). White adipocytes are unilocular cells containing a large central lipid vacuole, with a flattened nuclei located towards the periphery of the cell membrane. Non-esterified fatty acids (NEFA) accumulate in white adipocytes in the central vacuole and are
Brown adipose tissue
Adipose tissue is not exclusively white as new-born and hibernating mammals, for example, have a high abundance of brown adipose tissue (BAT) which provides protection from cold exposure by the generation of heat through non-shivering thermogenesis following the activation of uncoupling protein (UCP)1, a mitochondrial trans-membrane bound protein (Cannon and Nedergaard, 2012). Following the release of NEFA, UCP1 acts to allow a free-flow of protons across the inner mitochondrial membrane which
Sexual dimorphism and adipose tissue depot differences with obesity
The gender dimorphism in the development of WAT is best described in humans, with females possessing more fat than males irrespective of ethnicity, BMI and age (Gallagher et al., 2000). As summarised in Fig. 1, pre-menopausal females accumulate more subcutaneous WAT that is located primarily in peripheral and lower body areas, (i.e. subcutaneous, gluteal and femoral regions) (Lemieux et al., 1993, Ross et al., 1993), whereas males develop a higher abundance of visceral WAT in the upper body
Subcutaneous adipose tissue vs visceral adipose tissue
SAT is comprised of well organised, tightly packed spherical adipocytes, whereas VAT is highly vascularised with disorganised, irregular shaped lobules (Sniderman et al., 2007). Females possess larger subcutaneous than visceral adipocytes, suggesting a lower storage capacity in visceral depots for triglycerides, creating higher lipid saturation, increased lipolysis and greater susceptibility for dysfunction (Tchoukalova et al., 2008). Similarly, as reviewed by Tchernof et al. (2006), SAT cells
Adipose tissue and metabolic comorbidities
Epidemiological studies on cardiovascular and metabolic disease have identified that the abundance of both SAT and VAT are significantly correlated with blood pressure, plasma concentrations of glucose, triglycerides and high-density lipoprotein cholesterol which lead to increased risks of developing hypertension, T2DM and related metabolic comorbidities (Fox et al., 2007). Women, however, display a stronger relationship between VAT volume and the development of these risk factors than men (Fox
Sexual dimorphism in BAT deposition
In humans, there is currently insufficient data to determine whether a disparity exists between genders in BAT deposition. Males and females appear to possess a similar regional distribution of BAT, although when detected using FDG PET-CT, it was more prominent in the cervical-supraclavicular region in females, at a ratio of 2:1, compared to males (Cypess et al., 2009). This is explained primarily by the greater sensitivity to cold exposure by females (Quevedo et al., 1998), but it is uncertain
Obesity, metabolism and BAT
There is still a dearth of knowledge in the endocrine function of BAT, especially the small depots that remain in adults. A growing body of rodent work suggests that BAT could possess beneficial metabolic effects mediated by the production and release of endocrine signals, particularly during periods of increased thermogenesis (Villarroya et al., 2013). UCP1 knock-out mice exhibit increased weight gain in comparison to wild-type controls but only when housed under thermoneutral temperatures.
Inflammation associated with enhanced WAT mass
Hypertrophic white adipocytes increase the production and secretion of adipokines into the circulation, with adipokine gene expression positively correlated with adipocyte size (Skurk et al., 2007). Obesity and hyperinsulinaemia both stimulate the immune system, with raised insulin having a pleiotropic role to further promote lipid storage. The mechanisms mediating obesity induced insulin resistance remain complex and it is unsure whether insulin resistance is causally or negatively associated
Sex differences in obesity mediated inflammation
As previously discussed, different anatomical locations of WAT are heterogeneous between genders and in their metabolic profiles. Currently only a limited amount work exists in the field, but comparative studies analysing the effect of gender on the relationship between depots and their inflammatory profiles have identified that enlarged VAT contributes to elevated IL6 and CRP plasma concentrations (Beasley et al., 2009). The same study also demonstrated a trend for increased subcutaneous
Effect of the menopause
In morbidly obese women, those who demonstrated upper body obesity exhibited elevated plasma testosterone and estrone, yet lower body obesity was characterised by higher 17β-estradiol concentrations (Kirschner et al., 1990). Raised 17β-estradiol was inversely correlated to VAT mass and circulating inflammatory signalling molecules, but after the menopause these relationships were diminished with the reduction of oestrogen and increased appetite plus central adipose tissue expansion (
Sexual dimorphism of renal disease and HPA axis stimulation with obesity
The elevated chronic inflammatory status observed in obesity alongside its associated comorbidities is hypothesised to be a mechanism behind a more widespread systemic injury, targeting important organ systems within the body (Rocha and Libby, 2009). Moderate obesity in young adult sheep leads to enhanced inflammatory gene expression in the kidneys coupled with hypercellular invasion and expansion in the glomerular structure (Bloor et al., 2012). However, these responses were not observed in
Summary
A wealth of data has been reported supporting the existence of sexual dimorphism in the human population with the presence of obesity. Clarifying the multifaceted and complicated nature of regulation in adipose tissue deposition and its endocrine role in controlling the inflammatory and metabolic network is still uncertain. Both WAT and BAT appear to maintain dynamic endocrine roles which are linked to their anatomical locations, with different depots possessing diverse metabolic and
Acknowledgments
The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007–2013), project EarlyNutrition under grant agreement no. 289346.
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