Adiponectin reduces thermogenesis by inhibiting brown adipose tissue activation in mice

Abstract

Aims/hypothesis Adiponectin is an adipocyte-derived hormone that plays an important role in energy homeostasis. The main objective of this study was to investigate whether or not adiponectin regulates brown adipose tissue (BAT) activation and thermogenesis. Methods Core body temperatures (CBTs) of genetic mouse models were monitored at room temperature and during cold exposure. Cultured brown adipocytes and viral vector-mediated gene transduction were used to study the regulatory effects of adiponectin on Ucp1 gene expression and the underlying mechanisms. Results The CBTs of adiponectin knockout mice (Adipoq−/−) were significantly higher than those of wild type (WT) mice both at room temperature and during the cold (4°C) challenge. Conversely, reconstitution of adiponectin in Adipoq−/− mice significantly blunted β adrenergic receptor agonist-induced thermogenesis of interscapular BAT. After 10 days of intermittent cold exposure, Adipoq−/− mice exhibited higher UCP1 expression and more brown-like structure in inguinal fat than WT mice. Paradoxically, we found that the anti-thermogenic effect of adiponectin requires neither AdipoR1 nor AdipoR2, two well-known adiponectin receptors. In sharp contrast to the anti-thermogenic effects of adiponectin, AdipoR1 and especially AdipoR2 promote BAT activation. Mechanistically, adiponectin was found to inhibit Ucp1 gene expression by suppressing β3-adrenergic receptor expression in brown adipocytes. Conclusions/interpretation This study demonstrates that adiponectin suppresses thermogenesis, which is likely to be a mechanism whereby adiponectin reduces energy expenditure.

Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1

“…We used adenoviral vector-mediated in vivo gene transduction to reconstitute maternal adiponectin in Adipoq −/− dams [34]. Similar to in non-pregnant mice [34], adiponectin protein levels at 3 days after Ad- Adipoq viral vector injection were significantly increased in dam’s blood (data not shown). Our results showed that the body weight was significantly lower in fetuses from adiponectin-reconstituted dams compared with the fetuses from Ad- gfp -treated Adipoq −/− dams (Fig.…”

Metabolic shifts toward fatty-acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human APOE4

“…On the other hand, elevations in total adiponectin and in particular its most active high molecular weight multimer, were observed in APOE4 mice. Some studies have previously reported that adiponectin inhibits thermogenesis and UCP1 expression via a reduction in the supply of fatty acids to be used as thermogenic substrates 30,31 . In this study, we show that the presence of APOE4 is associated with increases in the percentage of lipid diverted to oxidation.…”

“…Moreover, increased expression of adiponectin receptors, which are positive regulators of UCP1 32 , was measured in the BAT of APOE4 mice. It has been proposed that adiponectin receptors may have other ligands or have ligand-independent activity 31 . Thus, the observed rise in adiponectin could simply be a consequence of reduced WAT mass, and may not be directly involved in the regulation of the metabolic switch observed in APOE4 mice…”

Adipose Tissue as an Endocrine Organ

“…It may on one hand acts on M2 macrophages by promoting their de novo proliferation; while on the other hand promotes mitochondrial biogenesis, insulin signaling, and the AMPK-SIRT1 pathway and up-regulates β3-adrenergic receptor in BAT [76]. However, it should be notified that opposite findings were also reported [77] and whether the inconsistencies were caused by the different strains of mice used, or gut microbiota in different housing environment, needs to be investigated in future.…”