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Depression: 21st Century Solutions + The Dark Side of Wheat

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Abstract Title:

Carnitine induces autophagy and restores high-fat diet-induced mitochondrial dysfunction.

Abstract Source:

Metabolism. 2017 Sep 28. Epub 2017 Sep 28. PMID: 28966077

Abstract Author(s):

Jin Woo Choi, Jung Hun Ohn, Hye Seung Jung, Young Joo Park, Hak Chul Jang, Sung Soo Chung, Kyong Soo Park

Article Affiliation:

Jin Woo Choi

Abstract:

OBJECTIVE: Autophagy is suppressed in skeletal muscle and the liver with insulin resistance induced by a high-fat diet. Autophagy is essential for maintaining mitochondrial function, and dysfunctional mitochondria are associated with insulin resistance. As carnitine treatment is well known to improve insulin resistance by promoting mitochondrial function, we investigated if carnitine affects autophagy in the skeletal muscle of a high-fat diet-induced rodent model of obesity.

RESULTS: After 6 weeks on a high-fat diet (48 kcal% fat), mice developed glucose intolerance, and the gastrocnemius muscle showed a decrease in insulin signaling and mitochondrial function, which was reversed after carnitine (100 mg/kg/day) treatment by oral gavage for 2 weeks. Swollen mitochondria with destroyed cristae were observed in the skeletal muscle of high-fat diet-fed mice but were not there after carnitine treatment. High-fat diet decreased LC3B-II, a marker of autophagosome formation, and increased sequestosome 1 (SQSTM1), expression of which was reversed after carnitine treatment. In C2C12 myotubes, prolonged treatment with palmitate suppressed autophagy, which was relieved by carnitine treatment. However, the induction of autophagy by carnitine in C2C12 myotubes was not observed after knock-down of peroxisome proliferator-activated receptorγ (PPARγ), which is known to regulate autophagy.

CONCLUSION: We conclude that the removal of dysfunctional mitochondria by induction of autophagy through PPARγ may be a novel mechanism by which carnitine improves insulin resistance and mitochondrial dysfunction in obesity.

Study Type : Animal Study

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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