Sexual Dimorphisms in Adult Human Brown Adipose Tissue

Abstract

OBESITY BIOLOGY AND INTEGRATED PHYSIOLOGY Study ImportanceWhat is already known?► Brown adipose tissue (BAT) expends energy in the form of heat and is therefore a potential target for therapeutic interventions to address obesity and metabolic disease. ► Sexual dimorphisms exist in terms of general adiposity and metabolism. ► Most BAT studies are conducted in rodents; most quantitative clinical trials of human BAT have been conducted in men.What does this study add?► We conducted a quantitative analysis of cold-induced BAT in healthy, lean, young women and men to explore the differences in amount, activity, and anatomical distribution. ► Women have less BAT volume than men, but the relative amount, metabolic activity, and distribution of detectable BAT are similar. ► Superficial dorsocervical adipose tissue with BAT-like glucose uptake is more prevalent in women and is a probable remnant of interscapular BAT seen in rodents and human newborns.Objective: This study aimed to quantify and compare the amount, activity, and anatomical distribution of cold-activated brown adipose tissue (BAT) in healthy, young, lean women and men. Methods: BAT volume and 18 F-fluorodeoxyglucose uptake were measured by positron emission tomography and computerized tomography in 12 women and 12 men (BMI 18.5-25 kg/m 2 , aged 18-35 years) after 5 hours of exposure to their coldest temperature before overt shivering.Results: Women had a lower detectable BAT volume than men (P = 0.03), but there was no difference after normalizing to body size. The mean BAT glucose uptake and relative distribution of BAT did not differ by sex. 18 F-fluorodeoxyglucose uptake consistent with BAT was observed in superficial dorsocervical adipose tissue of 6 of 12 women but only 1 of 12 men (P = 0.02). This potential BAT depot would pose fewer biopsy risks than other depots. Conclusions: Despite differences in adiposity and total BAT volume, we found that healthy, lean, young women and men do not differ in the relative amount, glucose uptake, and distribution of BAT. Dorsocervical 18 F-fluorodeoxyglucose uptake was more prevalent in women and may be a remnant of interscapular BAT seen in human newborns. Future studies are needed to discern how BAT contributes to whole-body thermal physiology and body weight regulation in women and men.Obesity (2020) 28, 241-246.

Effect of sex and sex steroids on brown adipose tissue heat production in humans

“…Previous studies have shown that, in response to very mild cold exposure (23°C), the increase in metabolic rate is also attenuated in women during the follicular phase relative to the luteal phase of the menstrual cycle (30). Indeed, a recent cold acclimation study suggested that 18 F-FDG uptake within the supraclavicular region was similar in men and women, but this work only characterised women during the follicular phase of the menstrual cycle (15). Together these studies, along with the current work, highlight the importance of the stage of menstrual cycle and thus the possible role of endogenous sex steroids in modulating metabolic responses to cold.…”

“…Despite this, a recent prospective study using PET-CT imaging suggested that women had a lower supraclavicular BAT volume than men, albeit 18 F-FDG uptake being comparable in men and women suggesting that overall supraclavicular BAT activity is similar, irrespective of sex (15). The study of Fletcher et al, however, identified a BAT depot in the superficial dorsocervical region that was more prevalent in women than men (15). Therefore, there appears to be sexual dimorphism in the distribution and activity of BAT, but whether this tissue exerts greater metabolic action in men or women remains to be elucidated.…”

“…Retrospective PET-CT studies suggest a greater prevalence of active BAT in women than in men (12) and data from animal models show that estrogen treatment increases thermogenesis in both BAT and skeletal muscle (13,14). Despite this, a recent prospective study using PET-CT imaging suggested that women had a lower supraclavicular BAT volume than men, albeit 18 F-FDG uptake being comparable in men and women suggesting that overall supraclavicular BAT activity is similar, irrespective of sex (15). The study of Fletcher et al, however, identified a BAT depot in the superficial dorsocervical region that was more prevalent in women than men (15).…”

“…This may be due, in part, to the changes in vasomotor control of blood flow to the skin (18), but it remains possible that alterations in thermogenesis contribute to changes in body temperature in women during different phases of the menstrual cycle. Indeed, the previous study of Fletcher et al (15) examined women during the follicular phase only. In vitro studies have suggested that progesterone may act directly at brown adipocytes, whereby progesterone treatment increases Ucp1 mRNA expression (19) and enhances noradrenalineinduced lipolysis in cultured brown adipocytes (20), thus emphasising the possible importance of the stage of cycle.…”

Feeding brown fat: dietary phytochemicals targeting non-shivering thermogenesis to control body weight

“…Contrarily, Fletcher et al . (26) could not confirm differences in cold-induced BAT activity or BAT distribution in healthy men v. women and the apparent higher BAT volume in men vanished after normalisation to body size (26) .…”