The capacity for oestrogen to influence obesity through brown adipose tissue thermogenesis in animal models: A systematic review and meta-analysis

Abstract

Pharmacological interventions to aid weight loss have historically targeted either appetite suppression or increased metabolic rate. Brown adipose tissue (BAT) possesses the capacity to expend energy in a futile cycle, thus increasing basal metabolic rate. In animal models, oestrogen has been implicated in the regulation of body weight, and it is hypothesized that oestrogen is acting by modulating BAT metabolism. A systematic search was performed, to identify research articles implementing in vivo oestrogen-related interventions and reporting outcome measures that provide direct or indirect measures of BAT metabolism. Meta-analyses were conducted where sufficient data were available. The final library of 67 articles were predominantly in rodent models and provided mostly indirect measures of BAT metabolism. Results of this review found that oestrogen's effects on body weight, in rats and possibly mice, are likely facilitated by both metabolic and appetitive mechanisms but are largely only found in ovariectomized models. There is a need for further studies to clarify the potential effects of oestrogen on BAT metabolism in gonad-intact and castrated male animal models.

Keywords: Animal models; brown adipose tissue; oestrogen; thermogenesis.

Figure 1

A flow chart illustrating proposed physiological responses to removal of endogenous oestrogen. From top to bottom: It is proposed that decreased oestrogen levels cause changes in both the hypothalamus and BAT. Hypothalamic levels of POMC decrease, leading to an increase in food intake, while increased hypothalamic AMPK causes increase sympathetic activity. In parallel to hypothalamic changes, mitochondrial biogenesis and β3‐AR expression are decreased in BAT. These parallel changes in BAT and the hypothalamus both contribute to decreased BAT thermogenesis. Outcome measures used experimentally to infer decreased BAT thermogenesis are shown radially around the “decreased BAT thermogenesis” bubble. Solid arrows indicate outcome measures more directly linked with BAT thermogenesis, while striped arrows represent intermediate steps, and thus a more indirect relationship. Direction of arrows infers direction of causality. AMPK, adenosine monophosphate‐activated protein kinase; BAT, brown adipose tissue; POMC, pro‐opiomelanocortin; RER, respiratory exchange ratio; UCP1, uncoupling protein 1

Figure 2

PRISMA flowchart summarizing the yield of the search strategy and screening procedures

Figure 3

Effect of oestrogen (experimental) on attenuation of body weight gain between ovariectomized female rats

Figure 4

Effect of oestrogen (experimental) on attenuation of body weight gain between ovariectomized female mice

Figure 5

Effect of oestrogen (experimental) on attenuation of body weight gain between gonad‐intact female mice and rats

Figure 6

Effect of oestrogen (experimental) on attenuation of body weight gain between gonad‐intact male mice and rats

Figure 7

Effect of oestrogen (experimental) on food intake between ovariectomized female mice and rats