Exercise training prevents skeletal muscle plasma membrane cholesterol accumulation, cortical actin filament loss, and insulin resistance in C57BL/6J mice fed a western-style high-fat diet

Ashley G. Ambery, Lixuan Tackett, Brent A. Penque, Joseph T. Brozinick, Jeffrey Elmendorf

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Insulin action and glucose disposal are enhanced by exercise, yet the mechanisms involved remain imperfectly understood. While the causes of skeletal muscle insulin resistance also remain poorly understood, new evidence suggest excess plasma membrane (PM) cholesterol may contribute by damaging the cortical filamentous actin (F-actin) structure essential for GLUT4 glucose transporter redistribution to the PM upon insulin stimulation. Here, we investigated whether PM cholesterol toxicity was mitigated by exercise. Male C57BL/6J mice were placed on low-fat (LF, 10% kCal) or high-fat (HF, 45% kCal) diets for a total of 8 weeks. During the last 3 weeks of this LF/HF diet intervention, all mice were familiarized with a treadmill for 1 week and then either sham-exercised (0 m/min, 10% grade, 50 min) or exercised (13.5 m/min, 10% grade, 50 min) daily for 2 weeks. HF-feeding induced a significant gain in body mass by 3 weeks. Sham or chronic exercise did not affect food consumption, water intake, or body mass gain. Prior to sham and chronic exercise, “pre-intervention” glucose tolerance tests were performed on all animals and demonstrated that HF-fed mice were glucose intolerant. While sham exercise did not affect glucose tolerance in the LF or HF mice, exercised mice showed an improvement in glucose tolerance. Muscle from sham-exercised HF-fed mice showed a significant increase in PM cholesterol, loss of cortical F-actin, and decrease in insulin-stimulated glucose transport compared to sham-exercised LF-fed mice. These HF-fed skeletal muscle membrane/cytoskeletal abnormalities and insulin resistance were improved in exercised mice. These data reveal a new therapeutic aspect of exercise being regulation of skeletal muscle PM cholesterol homeostasis. Further studies on this mechanism of insulin resistance and the benefits of exercise on its prevention are needed.

Original languageEnglish (US)
Article numbere13363
JournalPhysiological Reports
Volume5
Issue number16
DOIs
StatePublished - Aug 1 2017

Fingerprint

High Fat Diet
Actin Cytoskeleton
Inbred C57BL Mouse
Insulin Resistance
Skeletal Muscle
Cholesterol
Cell Membrane
Exercise
Glucose
Insulin
Actins
Fats
Diet
Facilitative Glucose Transport Proteins
Glucose Tolerance Test
Drinking
Homeostasis
Food
Muscles
Membranes

Keywords

  • Actin
  • cholesterol
  • exercise
  • insulin

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

Exercise training prevents skeletal muscle plasma membrane cholesterol accumulation, cortical actin filament loss, and insulin resistance in C57BL/6J mice fed a western-style high-fat diet. / Ambery, Ashley G.; Tackett, Lixuan; Penque, Brent A.; Brozinick, Joseph T.; Elmendorf, Jeffrey.

In: Physiological Reports, Vol. 5, No. 16, e13363, 01.08.2017.

Research output: Contribution to journalArticle

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abstract = "Insulin action and glucose disposal are enhanced by exercise, yet the mechanisms involved remain imperfectly understood. While the causes of skeletal muscle insulin resistance also remain poorly understood, new evidence suggest excess plasma membrane (PM) cholesterol may contribute by damaging the cortical filamentous actin (F-actin) structure essential for GLUT4 glucose transporter redistribution to the PM upon insulin stimulation. Here, we investigated whether PM cholesterol toxicity was mitigated by exercise. Male C57BL/6J mice were placed on low-fat (LF, 10{\%} kCal) or high-fat (HF, 45{\%} kCal) diets for a total of 8 weeks. During the last 3 weeks of this LF/HF diet intervention, all mice were familiarized with a treadmill for 1 week and then either sham-exercised (0 m/min, 10{\%} grade, 50 min) or exercised (13.5 m/min, 10{\%} grade, 50 min) daily for 2 weeks. HF-feeding induced a significant gain in body mass by 3 weeks. Sham or chronic exercise did not affect food consumption, water intake, or body mass gain. Prior to sham and chronic exercise, “pre-intervention” glucose tolerance tests were performed on all animals and demonstrated that HF-fed mice were glucose intolerant. While sham exercise did not affect glucose tolerance in the LF or HF mice, exercised mice showed an improvement in glucose tolerance. Muscle from sham-exercised HF-fed mice showed a significant increase in PM cholesterol, loss of cortical F-actin, and decrease in insulin-stimulated glucose transport compared to sham-exercised LF-fed mice. These HF-fed skeletal muscle membrane/cytoskeletal abnormalities and insulin resistance were improved in exercised mice. These data reveal a new therapeutic aspect of exercise being regulation of skeletal muscle PM cholesterol homeostasis. Further studies on this mechanism of insulin resistance and the benefits of exercise on its prevention are needed.",
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