Short-term physical inactivity induces diacylglycerol accumulation and insulin resistance in muscle via lipin1 activation
Autor: | Keishoku Sakuraba, Naoko Kaga, Ryuzo Kawamori, Yoshifumi Tamura, Noriko Ueno, Shin-ichi Ikeda, Hirotaka Watada, Hikari Taka, Saori Kakehi, Atsushi Kubota, Tetsuya Shiuchi |
---|---|
Rok vydání: | 2021 |
Předmět: |
Adult
Male medicine.medical_specialty Time Factors Physiology Endocrinology Diabetes and Metabolism Phosphatidate Phosphatase Diglycerides Mice Young Adult Insulin resistance Physiology (medical) Internal medicine medicine Animals Humans Insulin Cast immobilization Muscle Skeletal Diacylglycerol kinase Chemistry Mechanism (biology) Skeletal muscle Insulin sensitivity medicine.disease Mice Inbred C57BL Casts Surgical medicine.anatomical_structure Endocrinology Hindlimb Suspension Insulin Resistance Sedentary Behavior Signal Transduction |
Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 321:E766-E781 |
ISSN: | 1522-1555 0193-1849 |
Popis: | Physical inactivity impairs muscle insulin sensitivity. However, its mechanism is unclear. To model physical inactivity, we applied 24-h hind-limb cast immobilization (HCI) to mice with normal or high-fat diet (HFD) and evaluated intramyocellular lipids and the insulin signaling pathway in the soleus muscle. Although 2-wk HFD alone did not alter intramyocellular diacylglycerol (IMDG) accumulation, HCI alone increased it by 1.9-fold and HCI after HFD further increased it by 3.3-fold. Parallel to this, we found increased protein kinase C ε (PKCε) activity, reduced insulin-induced 2-deoxyglucose (2-DOG) uptake, and reduced phosphorylation of insulin receptor β (IRβ) and Akt, key molecules for insulin signaling pathway. Lipin1, which converts phosphatidic acid to diacylglycerol, showed increase of its activity by HCI, and dominant-negative lipin1 expression in muscle prevented HCI-induced IMDG accumulation and impaired insulin-induced 2-DOG uptake. Furthermore, 24-h leg cast immobilization in human increased lipin1 expression. Thus, even short-term immobilization increases IMDG and impairs insulin sensitivity in muscle via enhanced lipin1 activity. |
Databáze: | OpenAIRE |
Externí odkaz: |