Adipocytes are distributed throughout the body in discrete depots and the intrinsic cellular and metabolic properties of different populations are shaped by the specific niches in which they reside. Whereas visceral adipocytes exist within the body?s core, other subpopulations, including subcutaneous, marrow and dermal adipocytes primarily exist in temperatures well below 37oC. Despite this, the role of environmental temperature has largely been neglected in our consideration of adipocyte molecular and functional characteristics. Hints within historical literature suggest that cooler adipose tissue temperatures are also associated with greater lipid unsaturation. We have found similar correlations in rodents and humans, with cooler distal marrow adipocytes having increased unsaturated lipid composition. Housing rats at thermoneutrality decreases formation of unsaturated lipids in triacylglycerols of marrow adipocytes within the distal tibia and caudal vertebra. Warmer temperature also decreases expression of Stearoyl CoA Desaturase I. Adaptation of cultured adipocytes to 31oC is associated with elevated oxygen consumption, altered nutrient selection, elevated anabolic and catabolic lipid metabolism, and a genetic program for cold-adaptation. We hypothesize that cold adaptation results in profound changes to gene expression and metabolism that allow adipocytes to function at temperatures well below 37oC. To test these hypotheses, we propose a series of specific aims that when successfully completed will provide fundamental insights into how cold-adapted adipocytes are functionally different from their warmer counterparts. These studies will help uncover novel mechanisms of adaptive thermogenesis and identify targets for pharmacologic interventions to increase energy expenditure and combat incidence of obesity and diabetes.

Public Health Relevance

Although most subcutaneous, dermal and marrow adipocytes primarily exist in temperatures well below 37oC, the role of environmental temperature has largely been neglected in our consideration of their molecular and functional characteristics. Our preliminary data indicate that adaptation of cultured adipocytes to cooler temperatures causes profound changes to their molecular and physiological characteristics. Further exploration of these adaptive mechanisms may help uncover novel mechanisms of adaptive thermogenesis and identify targets for pharmacologic interventions to increase energy expenditure and combat incidence of obesity and diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK121759-01A1
Application #
10050058
Study Section
Integrative Physiology of Obesity and Diabetes Study Section (IPOD)
Program Officer
Haft, Carol R
Project Start
2020-07-07
Project End
2025-05-31
Budget Start
2020-07-07
Budget End
2021-05-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Physiology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109