Transcriptome Profiles of the Liver in Two Cold-Exposed Sheep Breeds Revealed Different Mechanisms and Candidate Genes for Thermogenesis

Cold-induced thermogenesis plays an important role in the survival of lambs exposed to low air temperatures. The liver produces and mediates heat production in mammals; however, to date, little is known about the role of liver genes in cold-induced thermogenesis in lambs. In this study, the difference in the liver transcriptome between Altay and Hu ewe lambs was compared. Because of different backgrounds of the two breeds, we hypothesized that the transcriptome profiles of the liver would differ between breeds when exposed to cold. Cold-exposed Altay lambs activated 8 candidate genes (ACTA1, MYH1, MYH2, MYL1, MYL2, TNNC1, TNNC2, and TNNT3) involved in muscle shivering thermogenesis; 3 candidate genes (ATP2A1, SLN, and CKM) involved in muscle nonshivering thermogenesis related to the Ca2+ signal and creatine cycle; and 6 candidate genes (PFKM, ALDOC, PGAM2, ENO2, ENO3, and ENO4) involved in enhancing liver metabolism. In contrast, the liver may not act as the main tissue for thermogenesis in cold-exposed Hu lambs. We concluded that Altay lambs rely on liver-mediated shivering and nonshivering thermogenesis by muscle tissue to a greater extent than Hu lambs. Results from this study could provide a theoretical foundation for the breeding and production of cold-resistant lambs.

The Role of Nonshivering Thermogenesis Genes on Leptin Levels Regulation in Residents of the Coldest Region of Siberia

Leptin plays an important role in thermoregulation and is possibly associated with the microevolutionary processes of human adaptation to a cold climate. In this study, based on the Yakut population (n = 281 individuals) living in the coldest region of Siberia (t°minimum −71.2 °C), we analyze the serum leptin levels and data of 14 single nucleotide polymorphisms (SNPs) of 10 genes (UCP1, UCP2, UCP3, FNDC5, PPARGC1A, CIDEA, PTGS2, TRPV1, LEPR, BDNF) that are possibly involved in nonshivering thermogenesis processes. Our results demonstrate that from 14 studied SNPs of 10 genes, 2 SNPs (the TT rs3811787 genotype of the UCP1 gene and the GG rs6265 genotype of the BDNF gene) were associated with the elevated leptin levels in Yakut females (p < 0.05). Furthermore, of these two SNPs, the rs3811787 of the UCP1 gene demonstrated more indications of natural selection for cold climate adaptation. The prevalence gradient of the T-allele (rs3811787) of UCP1 increased from the south to the north across Eurasia, along the shore of the Arctic Ocean. Thereby, our study suggests the potential involvement of the UCP1 gene in the leptin-mediated thermoregulation mechanism, while the distribution of its allelic variants is probably related to human adaptation to a cold climate.

Analysis of polymorphism of SNP markers of genes involved in nonshivering thermogenesis, UCP1 (rs1800592), UCP2 (rs659366) and UCP3 (rs2075577) in Yakuts and Chukchi

Впервые был проведен анализ частот аллелей полиморфизмов генов UCP1 (rs1800592), UCP2 (rs659366) и UCP3 (rs2075577) в популяциях якутов и чукчей, проживающих в условиях экстремального климата Восточной Сибири. For the first time an analysis of the frequencies of alleles polymorphism of the genes UCP1 (rs1800592), UCP2 (rs659366) and UCP3 (rs2075577) were studied in the Yakut and Chukchi populations, living in the extreme climate of Eastern Siberia.

Uncoupling protein 1 and the capacity for nonshivering thermogenesis are components of the glucose homeostatic system

Uncoupling protein 1 (Ucp1) provides nonshivering thermogenesis (NST) fueled by the dissipation of energy from macronutrients in brown and brite adipocytes. The availability of thermogenic fuels is facilitated by the uptake of extracellular glucose. This conjunction renders thermogenic adipocytes in brown and white adipose tissue (WAT) a potential target against obesity and glucose intolerance. We employed wild-type (WT) and Ucp1-ablated mice to elucidate this relationship. In three experiments of similar setup, Ucp1-ablated mice fed a high-fat diet (HFD) had either reduced or similar body mass gain, food intake, and metabolic efficiency compared with WT mice, challenging the hypothesized role of this protein in the development of diet-induced obesity. Despite the absence of increased body mass, oral glucose tolerance was robustly impaired in Ucp1-ablated mice in response to HFD. Postprandial glucose uptake was attenuated in brown adipose tissue but enhanced in subcutaneous WAT of Ucp1-ablated mice. These differences were explainable by expression of the insulin-responsive member 4 of the facilitated glucose transporter family and fully in line with the capacity for NST in these very tissues. Thus, the postprandial glucose uptake of adipose tissues serves as a surrogate measure for Ucp1-dependent and independent capacity for NST. Collectively, our findings corroborate Ucp1 as a modulator of adipose tissue glucose uptake and systemic glucose homeostasis but challenge its hypothesized causal effect on the development of obesity.

mTOR signaling in Brown and Beige adipocytes: implications for thermogenesis and obesity

Brown and beige adipocytes are mainly responsible for nonshivering thermogenesis or heat production, despite the fact that they have distinguished features in distribution, developmental origin, and functional activation. As a nutrient sensor and critical regulator of energy metabolism, mechanistic target of rapamycin (mTOR) also plays an important role in the development and functional maintenance of adipocytes. While the recent studies support the notion that mTOR (mTORC1 and mTORC2) related signaling pathways are of great significance for thermogenesis and the development of brown and beige adipocytes, the exact roles of mTOR in heat production are controversial. The similarities and disparities in terms of thermogenesis might be ascribed to the use of different animal models and experimental systems, distinct features of brown and beige adipocytes, and the complexity of regulatory networks of mTORC1 and mTORC2 in energy metabolism.