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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #329829
Title: Diminished anabolic signaling responses to insulin induced by intramuscular lipid accumulation is associated with inflammation in aging but not obesity

Author
item RIVAS, DONATO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MCDONALD, DEVIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item RICE, NICHOLAS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item HARAN, PRASHANTH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item DOLNIKOWSKI, GREGORY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: American Journal of Physiology - Regulatory Integrative & Comparative Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/11/2016
Publication Date: 1/13/2016
Citation: Rivas, D.A., Mcdonald, D., Rice, N., Haran, P., Dolnikowski, G.G., Fielding, R.A. 2016. Diminished anabolic signaling responses to insulin induced by intramuscular lipid accumulation is associated with inflammation in aging but not obesity. American Journal of Physiology - Regulatory Integrative & Comparative Physiology. 310(7):R561-R569. doi: 10.1152/ajpregu.00198.

Interpretive Summary: The loss of skeletal muscle mass is observed in many conditions including, aging and obesity. The loss of muscle mass and function with aging is defined as sarcopenia and characterized by a mismatch between making muscle proteins and breaking down proteins. In both aging and obese muscle there are increases in the storage of fat within the muscle. Stored fat in the muscle may have a role in inability to make muscle protein leading to muscle loss in aging and obesity. In the present study, aged and high-fat fed mice were used to determine mechanisms leading to muscle loss. We hypothesized the storage of specific types of fat in skeletal muscle, such as, ceramide or diacylglycerols, leads to the inability to use insulin, a hormone that can control the ability to make muscle proteins, with aging and obesity. We report a positive association between specific fat stored in muscle and the loss of lean mass and muscle strength. Obesity and aging induced significantly higher storage of ceramide and diacylglycerol compared to young. Also there was a loss in the ability of aged and obese mice to respond to insulin compared to lean mice.

Technical Abstract: The loss of skeletal muscle mass is observed in many pathophysiological conditions including, aging and obesity. The loss of muscle mass and function with aging is defined as sarcopenia and characterized by a mismatch between skeletal muscle protein synthesis (MPS) and breakdown. Characteristic metabolic features of both aging and obese muscle are increases in intramyocellular lipid (IMCL) content. IMCL accumulation may play a mechanistic role in the development anabolic resistance and the progression of muscle atrophy in aging and obesity. In the present study, aged and high fat fed mice were used to determine mechanisms leading to muscle loss. We hypothesized the accumulation of bioactive lipids in skeletal muscle, such as, ceramide or diacylglycerols, leads to insulin resistance with aging and obesity and the inability to activate protein synthesis contributing to skeletal muscle loss. We report a positive association between bioactive lipid accumulation and the loss of lean mass and muscle strength. Obesity and aging induced significantly higher storage of ceramide and diacylglycerol compared to young. Furthermore, there was an attenuated insulin response to components of the mTOR anabolic signaling pathway. We also observed differential increases in the expression of inflammatory cytokines and the phosphorylation of IkBa between aging and obesity. These data challenge the accepted role of increased inflammation in obesity induced insulin resistance in skeletal muscle. Furthermore, we have now established IkBa with a novel function in aging associated muscle loss that may be independent of its previously understood role as an NFkB inhibitor.