Adams 2018 MiP2018

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Sean Adams
Long-chain acylcarnitines: New perspectives on bioactivities and trafficking.

Link: MiP2018

Adams SH (2018)

Event: MiP2018

COST Action MitoEAGLE

Long-chain fatty acids (LCFAs) are an important fuel for heart, skeletal muscle (especially type 1, myoglobin-rich, “slow-twitch” muscle), and liver. Combustion of LCFAs is facilitated by conversion of LCFA-CoAs to long-chain acylcarnitines (LCACs) by carnitine palmitoyltransferase 1 (CPT1) on the outer aspect of the mitochondrial membrane, followed by transport into the mitochondrion and retroconversion to LCFA-CoA by CPT2; the LCFA-CoA is then available for β-oxidation. The match between LCFA availability, conversion to LCACs, and β-oxidation is not perfect, leading in some cases to accumulation of LCACs in muscle—for instance, during exercise or type 2 diabetes. Inborn errors of β-oxidation enzymes can also lead to accumulation of LCACs and other lipids in tissues. A major question in the field of metabolic (patho)physiology is whether or not lipids such as LCACs serve as signaling molecules or “lipotoxins” under certain conditions. Several years ago, we made the proposal that some acylcarnitines activate inflammation in macrophages (and perhaps other tissues) and contribute to insulin resistance. Follow up research supported this assertion when LCACs were used to treat immune and muscle cells in culture, and others have shown that blockade of CPT1 in culture alleviates fat-induced insulin resistance. Other studies in our lab and those of others support the idea that LCACs have bioactivities including increasing intracellular calcium, neuronal activation, and mitochondrial dysfunction, possibly by acting through interaction with membranes. This talk will provide a retrospective overview of LCAC-associated cell stress responses, and will also highlight an emerging role for myoglobin as a LCFA/LCAC binding protein. We speculate that this interaction is important to control intracellular free concentrations and trafficking of LCACs and LCFAs, hence possibly playing a role in pathological and physiological actions of these lipids in skeletal muscle and cardiac myocytes.


Bioblast editor: Plangger M


Labels: MiParea: Exercise physiology;nutrition;life style  Pathology: Diabetes 



Regulation: Fatty acid 




Affiliations

Arkansas Children’s Nutrition Center and Univ Arkansas Medical Sciences, AR, USA

Support

Funding: NIH-NIDDK R01 DK 078328 - 01A1; R01DK078328 - 02S1; USDA-ARS Project 6026-51000-010-05S; American Diabetes Association (1-12-BS-02)