OBJECTIVE: Non-shivering thermogenesis (NST) mediated by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) can be activated via the adrenergic system in response to cold or diet, contributing to both thermal and energy homeostasis. Other mechanisms, including metabolism of skeletal muscle, may also be involved in NST. However, relative contribution of these energy dissipating pathways and their adaptability remain a matter of long-standing controversy. METHODS: We used warm-acclimated (30 °C) mice to characterize the effect of an up to 7-day cold acclimation (6 °C; CA) on thermoregulatory thermogenesis, comparing inbred mice with a genetic background conferring resistance (A/J) or susceptibility (C57BL/6 J) to obesity. RESULTS: Both warm-acclimated C57BL/6 J and A/J mice exhibited similar cold endurance, assessed as a capability to maintain core body temperature during acute exposure to cold, which improved in response to CA, resulting in comparable cold endurance and similar induction of UCP1 protein in BAT of mice of both genotypes. Despite this, adrenergic NST in BAT was induced only in C57BL/6 J, not in A/J mice subjected to CA. Cold tolerance phenotype of A/J mice subjected to CA was not based on increased shivering, improved insulation, or changes in physical activity. On the contrary, lipidomic, proteomic and gene expression analyses along with palmitoyl carnitine oxidation and cytochrome c oxidase activity revealed induction of lipid oxidation exclusively in skeletal muscle of A/J mice subjected to CA. These changes appear to be related to skeletal muscle NST, mediated by sarcolipin-induced uncoupling of sarco(endo)plasmic reticulum calcium ATPase pump activity and accentuated by changes in mitochondrial respiratory chain supercomplexes assembly. CONCLUSIONS: Our results suggest that NST in skeletal muscle could be adaptively augmented in the face of insufficient adrenergic NST in BAT, depending on the genetic background of the mice. It may provide both protection from cold and resistance to obesity, more effectively than BAT.

• Keywords
• Brown adipose tissue, Mitochondrial supercomplex, Non-shivering thermogenesis, Obesity, Sarcolipin, Skeletal muscle,
• MeSH
• Adrenergic Agents metabolism   MeSH
• Adipose Tissue, Brown * metabolism   MeSH
• Mice, Inbred Strains MeSH
• Muscle, Skeletal metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Obesity metabolism   MeSH
• Proteomics * MeSH
• Thermogenesis physiology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adrenergic Agents MeSH

To specify the role of adrenoceptors in mediating adrenergic functions after adaptation of humans to cold, effect of administration of increasing concentrations of beta1 and beta2 adrenomimetics (Dobutamine, Bricanyl) on resting metabolic rate, heart rate, systolic blood pressure, rectal and skin temperatures of control humans and of cold adapted winter swimmers was studied. Increase in metabolic rate, mediated by beta1 and beta2 adrenomimetics, was attenuated after cold adaptation, indicating downregulation of beta1 and beta2 adrenoceptors. Since cold adapted humans have greater capacity of nonshivering thermogenesis, than that mediated by both beta1 and beta2 adrenoceptors, the role of other subtypes of adrenoceptors in mediating nonshivering thermogenesis is anticipated. Heart rate increased after administration of the beta2 agonist, but was not influenced by the beta1 agonist. The significance of beta2 adrenoceptors in mediating heart rate was depressed after cold adaptation. Data indicate that modifications of activity of beta adrenoceptors play crucial role in mechanisms responsible for adaptation of humans to cold.

• MeSH
• Receptors, Adrenergic drug effects   physiology   MeSH
• Adrenergic beta-Agonists pharmacology   MeSH
• Adrenergic beta-1 Receptor Agonists MeSH
• Adrenergic beta-2 Receptor Agonists MeSH
• Receptors, Adrenergic, beta-1 physiology   MeSH
• Receptors, Adrenergic, beta-2 physiology   MeSH
• Dobutamine pharmacology   MeSH
• Adult MeSH
• Adaptation, Physiological drug effects   physiology   MeSH
• Infusions, Intravenous MeSH
• Blood Pressure drug effects   physiology   MeSH
• Humans MeSH
• Metabolism drug effects   physiology   MeSH
• Cold Temperature * MeSH
• Swimming physiology   MeSH
• Oxygen Consumption drug effects   physiology   MeSH
• Heart Rate drug effects   physiology   MeSH
• Sympathetic Nervous System drug effects   physiology   MeSH
• Skin Temperature drug effects   physiology   MeSH
• Terbutaline pharmacology   MeSH
• Thermogenesis drug effects   physiology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Receptors, Adrenergic MeSH
• Adrenergic beta-Agonists MeSH
• Adrenergic beta-1 Receptor Agonists MeSH
• Adrenergic beta-2 Receptor Agonists MeSH
• Receptors, Adrenergic, beta-1 MeSH
• Receptors, Adrenergic, beta-2 MeSH
• Dobutamine MeSH
• Terbutaline MeSH