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Published on: June 12, 2020
UCP1-independent thermogenesis in white adipose tissue of cold-acclimated Ucp1-/- mice
Jozef Ukropec1, Rea P Anunciado, Yann Ravussin
1Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808, USA.
Abstract:
Apart from UCP1-based nonshivering thermogenesis in brown adipocytes, the identity of thermogenic mechanisms that can be activated to reduce a positive energy balance is largely unknown. To identify potentially useful mechanisms, we have analyzed physiological and molecular mechanisms that enable mice, genetically deficient in UCP1 and sensitive to acute exposure to the cold at 4 degrees C, to adapt to long term exposure at 4 degrees C. UCP1-deficient mice that can adapt to the cold have increased oxygen consumption and show increased oxidation of both fat and glucose as indicated from serum metabolite levels and liver glycogen content. Enhanced energy metabolism in inguinal fat was also indicated by increased oxygen consumption and fat oxidation in tissue suspensions and increased AMP kinase activity in dissected tissues. Analysis of gene expression in skeletal muscle showed surprisingly little change between cold-adapted Ucp1+/+ and Ucp1-/- mice, whereas in inguinal fat a robust induction occurred for type 2 deiodinase, sarcoendoplasmic reticulum Ca2+-ATPase, mitochondrial glycerol 3-phosphate dehydrogenase, PGC1alpha, CoxII, and mitochondrial DNA content. Western blot analysis showed an induction of total phospholamban and its phosphorylated form in inguinal fat and other white fat depots, but no induction was apparent in muscle. We conclude that alternative thermogenic mechanisms, based in part upon the enhanced capacity for ion and substrate cycling associated with brown adipocytes in white fat depots, are induced in UCP1-deficient mice by gradual cold adaptation.
Insights
Uncoupling protein 1 (UCP1)-deficient mice adapt to cold by activating alternative thermogenic mechanisms in white fat. This involves increased energy metabolism and ion cycling, revealing new pathways for managing energy balance.
Area of Science:
- Metabolic research
- Thermogenesis
- Obesity research
Background:
- The mechanisms of thermogenesis beyond UCP1 in brown adipocytes are not fully understood.
- Identifying alternative thermogenic pathways is crucial for reducing positive energy balance and combating obesity.
Purpose of the Study:
- To investigate the physiological and molecular adaptations in UCP1-deficient mice during cold adaptation.
- To identify novel thermogenic mechanisms activated in the absence of UCP1.
Main Methods:
- Analysis of physiological parameters (oxygen consumption, metabolite levels, glycogen content) in UCP1-deficient mice exposed to cold.
- Gene expression and Western blot analysis in skeletal muscle and inguinal fat.
- Measurement of AMP kinase activity in dissected tissues.
Main Results:
- UCP1-deficient mice adapted to cold exhibited increased oxygen consumption and enhanced fat and glucose oxidation.
- Inguinal fat showed increased energy metabolism, AMP kinase activity, and robust induction of genes like type 2 deiodinase and PGC1alpha.
- White fat depots, but not muscle, showed increased phospholamban, suggesting ion cycling contributes to thermogenesis.
Conclusions:
- Gradual cold adaptation in UCP1-deficient mice induces alternative thermogenic mechanisms.
- These mechanisms are partly based on enhanced ion and substrate cycling within white fat depots, mimicking brown adipocyte functions.
- This highlights the plasticity of white adipose tissue in contributing to energy expenditure.
