Microbiota Depletion Impairs Thermogenesis of Brown Adipose Tissue and Browning of White Adipose Tissue

Abstract

Graphical AbstractHighlights d Mice lacking gut microbiota have impaired UCP1-dependent thermogenesis in cold d These effects are replicated in germ-free mice treated with CL-316243 d IL-4 has no differential effect on energy metabolism in either control or ABX mice d Gavage of ABX mice with butyrate partially rescues the effects on BAT recruitment SUMMARYThe relation between gut microbiota and the host has been suggested to benefit metabolic homeostasis. Brown adipose tissue (BAT) and beige adipocytes facilitate thermogenesis to maintain host core body temperature during cold exposure. However, the potential impact of gut microbiota on the thermogenic process is confused. Here, we evaluated how BAT and white adipose tissue (WAT) responded to temperature challenges in mice lacking gut microbiota. We found that microbiota depletion via treatment with different cocktails of antibiotics (ABX) or in germfree (GF) mice impaired the thermogenic capacity of BAT by blunting the increase in the expression of uncoupling protein 1 (UCP1) and reducing the browning process of WAT. Gavage of the bacterial metabolite butyrate increased the thermogenic capacity of ABX-treated mice, reversing the deficit. Our results indicate that gut microbiota contributes to upregulated thermogenesis in the cold environment and that this may be partially mediated via butyrate.

Inter‐organ communication: a gatekeeper for metabolic health

“…In addition, Mills and colleagues demonstrated that succinate accumulates in BAT upon cold exposure and favors thermogenesis in an UCP1-dependent manner [164]. Furthermore, gut microbiota has been described in the past two decades as a very important player in the regulation of whole-body energy homeostasis, in response to diverse stimuli such as cold [165,166], nutrition [167,168], or fasting/feeding cycles [168][169][170], through the production of mediators such as short chain fatty acids (SCFAs) and secondary BAs [167,169].…”

The Role of the Gut Microbiome in Energy Balance With a Focus on the Gut-Adipose Tissue Axis

“…Additionally, there are beige, or brite, adipocytes, which are an inducible form of brown adipocytes that are sporadically generated within white adipose tissue in response to various stimuli such as cold temperatures (Sidossis and Kajimura, 2015). Accumulating evidence suggests that the gut microbiome affects the thermogenic capacity of brown fat and the formation of beige adipocytes (Suárez-Zamorano et al, 2015;Li et al, 2019). For example, when Suárez-Zamorano et al (2015) depleted the microbiota of wild-type C57Bl/6J mice by administering antibiotic cocktails, the mice had more beige adipocytes in subcutaneous and perigonadal white adipose tissues (WATs) than did untreated controls.…”

The microbiota and immune‐mediated diseases: Opportunities for therapeutic intervention

“…The microbiota can affect adaptive thermogenesis, which is regulated by brown adipose tissue, but is reduced in obesity [69]. Depletion of the microbiota with a cocktail of antibiotics suppressed the thermogenic capacity of brown adipose tissue by inhibiting expression of uncoupling protein 1 and reducing the browning of white adipose tissue [69]. This defect was reversed by oral administration of butyrate, suggesting that this anti-inflammatory metabolite of certain gut bacteria can help to maintain thermogenesis.…”