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

Authors: WEI, QIONG - Children'S Nutrition Research Center (CNRC); LEE, JONG - Children'S Nutrition Research Center (CNRC); WANG, HONGYING - Texas A&M University; BONGMBA, ODELIA Y - Children'S Nutrition Research Center (CNRC); WU, CHIA-SHAN - Texas A&M University; PRADHAN, GEETALI - Children'S Nutrition Research Center (CNRC); SUN, XILLIN - Southeast University; CHEW, LINDSEY - Baylor College Of Medicine; BAJAJ, MANDEEP - Baylor College Of Medicine; CHAN, LAWRENCE - Baylor College Of Medicine; CHAPKIN, ROBERTS - Texas A&M University; CHEN, MIAO-HSUEH - Children'S Nutrition Research Center (CNRC); SUN, YUXIANG - Children'S Nutrition Research Center (CNRC)

Submitted to: Biomed Central Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/12/2017
Publication Date: 10/23/2017
Citation: Wei, Q., Lee, J.H., Wang, H., Bongmba, O.N., Wu, C., Pradhan, G., Sun, X., Chew, L., Bajaj, M., Chan, L., Chapkin, R., Chen, M., Sun, Y. 2017. Adiponectin is required for maintaining normal body temperature in a cold environment. Biomed Central Physiology. https://doi.org/10.1186/s12899-017-0034-7.
DOI: https://doi.org/10.1186/s12899-017-0034-7

Interpretive Summary: Temperature dysfunction in the body promotes obesity and insulin resistance. Adiponectin is an important regulator of energy balance. In this study, we investigated the role of adiponectin in thermo-dysfunction using a mouse model that lacks adiponectin. We found that under normal housing temperature of 24 degree C normal housing condition, the body weight the of the adiponectin deficient mice were unchanged. Conversely, under 4 degree C cold exposure, the mice exhibited reduced body temperature, and showed reduced expression of genes governing temperature regulation in heat-producing fat tissues. Our findings demonstrate that adiponectin is an essential regulator of temperature control, and adiponectin is required for maintaining body temperature under cold exposure.

Technical Abstract: 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 -/-). 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. Under normal housing temperature of 24 degree 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 B3-adrenergic receptor, insulin signaling, and the AMPK-SIRT1 pathway in BAT. Our findings demonstrate that adiponectin is an essential regulator of thermogenesis, and adiponectin is required for maintaining body temperature under cold exposure.