Background: Thermogenic impairment promotes obesity and insulin resistance. Adiponectin is an important
regulator of energy homeostasis. While many beneficial metabolic effects of adiponectin resemble that of
activated thermogenesis, the role of adiponectin in thermogenesis is not clear. In this study, we investigated the
role of adiponectin in thermogenesis using adiponectin-null mice (Adipoq−/−).
Methods: Body composition was measured using EchoMRI. Metabolic parameters were determined by indirect
calorimetry. Insulin sensitivity was evaluated by glucose- and insulin- tolerance tests. Core body temperature was
measured by a TH-8 temperature monitoring system. Gene expression was assessed by real-time PCR and protein
levels were analyzed by Western blotting and immunohistochemistry. The mitochondrial density of brown adipose
tissue was quantified by calculating the ratio of mtDNA:total nuclear DNA.
Results: Under normal housing temperature of 24 °C and ad libitum feeding condition, the body weight, body
composition, and metabolic profile of Adipoq−/− mice were unchanged. Under fasting condition, Adipoq−/− mice
exhibited reduced energy expenditure. Conversely, under cold exposure, Adipoq−/− mice exhibited reduced body
temperature, and the expression of thermogenic regulatory genes was significantly reduced in brown adipose
tissue (BAT) and subcutaneous white adipose tissue (WAT). Moreover, we observed that mitochondrial content
was reduced in BAT and subcutaneous WAT, and the expression of mitochondrial fusion genes was decreased in
BAT of Adipoq−/− mice, suggesting that adiponectin ablation diminishes mitochondrial biogenesis and altered
mitochondrial dynamics. Our study further revealed that adiponectin deletion suppresses adrenergic activation,
and down-regulates β3-adrenergic receptor, insulin signaling, and the AMPK-SIRT1 pathway in BAT.
Conclusions: Our findings demonstrate that adiponectin is an essential regulator of thermogenesis, and adiponectin
is required for maintaining body temperature under cold exposure.

• Adiponectin is required for maintaining normal body temperature in a cold environment