Excess Membrane Cholesterol is an Early Contributing Reversible Aspect of Skeletal Muscle Insulin Resistance in C57BL/6NJ Mice Fed a Western-Style High-Fat Diet.

Excess Membrane Cholesterol is an Early Contributing Reversible Aspect of Skeletal Muscle Insulin Resistance in C57BL/6NJ Mice Fed a Western-Style High-Fat Diet. Am J Physiol Endocrinol Metab. 2019 Jun 25;: Authors: Grice BA, Barton KJ, Covert JD, Kreilach AM, Tackett L, Brozinick JT, Elmendorf JS Abstract Skeletal muscle insulin resistance manifests shortly after high-fat feeding, yet mechanisms are not known. Here we set out to determine whether excess skeletal muscle membrane cholesterol and cytoskeletal derangement known to compromise glucose transporter GLUT4 regulation occurs early after high-fat feeding. We fed six-week old male C57BL/6NJ mice either a low-fat (LF, 10% kcal) or high-fat (HF, 45% kcal) diet for one week. This HF-feeding challenge was associated with an increase, albeit slight, in body mass, glucose intolerance and hyperinsulinemia. Liver analyses did not reveal signs of hepatic insulin resistance; however, skeletal muscle immunoblots of triad-enriched regions containing transverse tubule membrane showed a marked loss of stimulated GLUT4 recruitment. An increase in cholesterol was also found in these fractions from HF-fed mice. These derangements were associated with a marked loss of cortical filamentous actin (F-actin) that is essential for GLUT4 regulation and known to be compromised by increases in membrane cholesterol. Both the withdrawal of the HF diet, or two subcutaneous injections of the cholesterol-lowe...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research