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

https://doi.org/10.1016/j.yhbeh.2014.02.007Get rights and content

Highlights

  • Endocrine and inflammatory signalling roles of white and brown adipose tissue.

  • Influence of sex on adipose deposition prior to and during the development obesity.

  • Differences in metabolic and physiological roles of central and peripheral adipose tissues.

  • Current knowledge on brown adipose tissue deposition and activity with gender and obesity.

  • Role of HPA activation in sexual dimorphism with obesity.

Abstract

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.

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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