Altered Lipid Metabolism Impairs Skeletal Muscle Force in Young Rats Submitted to a Short-Term High-Fat Diet

Objective Obesity is becoming increasingly prevalent and is an important contributor to the worldwide burden of diseases. It is widely accepted that exercise training is beneficial for the prevention and treatment of obesity. However, the underlying mechanism by which exercise training improving skeletal muscle lipid metabolism is still not fully described. Sestrins (Sestrin1-3) are highly conserved stress-inducible protein. Concomitant ablation of Sestrin2 and Sestrin3 has been reported to provoke hepatic mTORC1/S6K1 activation and insulin resistance even without nutritional overload and obesity, implicating that Sestrin2 and Sestrin3 have an important homeostatic function in the control of mammalian glucose and lipid metabolism. Our previous results demonstrated that physical exercise increased Sestrin2 expression in murine skeletal muscle, while the role of Sestrin2 in regulating lipid metabolism remains unknown. SH2 domain containing inositol 5-phosphatase (SHIP2) acts as a negative regulator of the insulin signaling both in vitro and in vivo. An increased expression of SHIP2 inhibits the insulin-induced Akt activation, glucose uptake, and glycogen synthesis in 3T3-L1 adipocytes, L6 myotubes and tissues of animal models. Alterations of SHIP2 expression and/or enzymatic function appear to have a profound impact on the development of insulin resistance. However, the regulatory function of SHIP2 in lipid metabolism after exercise remains unclear. It has been reported that SHIP2 modulated lipid metabolism through regulating the activity of c-Jun N-terminal kinase (JNK) and Sterol regulatory element-binding protein-1 (SREBP-1). JNK is a subclass of mitogen-activated protein kinase (MAPK) signaling pathway in mammalian cells and plays a crucial role in metabolic changes and inflammation associated with a high-fat diet. Inhibition of JNK reduces lipid deposition and proteins level of fatty acid de novo synthesis in liver cells. It has been reported that Sestrin2 regulated the phosphorylation of JNK, however the underlying mechanism remains unclear. SREBP-1 is important in regulating cholesterol biosynthesis and uptake and fatty acid biosynthesis, and SREBP-1 expression produces two different isoforms, SREBP-1a and SREBP-1c. SREBP-1c is responsible for regulating the genes required for de novo lipogenesis and its expression is regulated by insulin. SREBP-1a regulates genes related to lipid and cholesterol production and its activity is regulated by sterol levels in the cell. Altogether, the purpose of this study was to explore the effect and underlying mechanism of Sestrin2 on lipid accumulation after exercise training. Methods Male wild type and SESN2−/− mice were divided into normal chow (NC) and high-fat diet (HFD) groups to create insulin resistance mice model. After 8 weeks the IR model group was then divided into HFD sedentary control and HFD exercise groups (HE). Mice in HE group underwent 6-week treadmill exercise to reveal the effect of exercise training on lipid metabolism in insulin resistance model induced by HFD. We explored the mechanism through which Sestrin2 regulated lipid metabolism in vitro by supplying palmitate, overexpressing or inhibiting SESNs, SHIP2 and JNK in myotubes. Results We found that 6-week exercise training decreased body weight, BMI and fat mass in wild type and SESN2-/- mice after high-fat diet (HFD) feeding. And exercise training decreased the level of plasma glucose, serum insulin, triglycerides and free fatty acids in wild type but not in Sestrin2-/- mice. Lipid droplet in skeletal muscle was also decreased in wild type but did not in Sestrin2-/- mice. Moreover, exercise training increased the proteins expression involved in fatty acid oxidation and decreased the proteins which related to fatty acid de novo synthesis. The results of oil red staining and the change of proteins related to fatty acid de novo synthesis and beta oxidation in myotubes treated with palmitate, Ad-SESN2 and siRNA-Sestrin2 were consisted with the results in vivo, which suggested that Sestrin2 was a key regulator in lipid metabolism. Exercise training increased Sestrin2 expression and reversed up-regulation of SHIP2 and pJNK induced by HFD in wild type mice but not in Sestrin2-/- mice. In parallel, overexpression of Sestrin2 decreased the level of SHIP2 and pJNK induced by palmitate while Sestrin2 knock down by siRNA-Sestrin2 treatment did not change the expression of SHIP2 and pJNK, which suggested that Sestrin2 modulated SHIP2 and JNK in the state of abnormal lipid metabolism. Inhibition of SHIP2 reduced the activity of JNK, increased lipid accumulation and the proteins of fatty acid synthesis after palmitate treatment and over expression of Sestrin2, which suggest that Sestrin2 modulated lipid metabolism through SHIP2/JNK pathway. Conclusions Sestrin2 plays an important role in improving lipid metabolism after exercise training, and Sestrin2 regulates lipid metabolism by SHIP2-JNK pathway in skeletal muscle.

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ALTERED LIPID METABOLISM IN PRIMARY CULTURES OF SKELETAL MUSCLE FROM HUMANS DIAGNOSED AS MALIGNANT HYPERTHERMIA SUSCEPTIBLE

Anesthesiology ◽

10.1097/00000542-199109001-00637 ◽

1991 ◽

Vol 75 (3) ◽

pp. A638-A638

Author(s):

J E Fletcher ◽

M-S Jiang ◽

Q-H Gong ◽

H Rosenberg

Keyword(s):

Skeletal Muscle ◽

Lipid Metabolism ◽

Malignant Hyperthermia ◽

Primary Cultures ◽

Malignant Hyperthermia Susceptible ◽

Altered Lipid Metabolism ◽

Altered Lipid

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Erchen Decoction Mitigates Lipid Metabolism Disorder by the Regulation of PPARγ and LPL Gene in a High-Fat Diet C57BL/6 Mice Model

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9102475 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Mengting Zhang ◽

Yanfei Shao ◽

Bizhen Gao ◽

Jicheng Chen ◽

Ping Zhang ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Lipid Metabolism ◽

Visceral Fat ◽

Protein Level ◽

High Fat Diet ◽

Blood Lipid ◽

Abdominal Circumference ◽

High Fat ◽

Gene And Protein Expression

Erchen decoction (ECD) is a common treatment prescribed in traditional Chinese medicine (TCM) clinics, which has remarkable efficacy in the treatment of obesity, fatty liver, hyperlipidemia, diabetes, and other diseases caused by phlegm. In this study, we investigated the effect that ECD had on the lipid metabolism induced by high-fat diet in C57BL/6 mice. Body weight, body length, and abdominal circumference were detected. Blood lipid content was measured via biochemical assay kit. The gene and protein expression of PPARγ and LPL in visceral fat and skeletal muscle of mice was measured by real-time PCR and western blot. The research discovered that the phlegm-resolving effect that ECD had on high-fat diet mice was mainly manifested as reduced body weight, Lee’s index, abdominal circumference, and level of TG and TC. Meanwhile, we observed significantly increased PPARγ mRNA and protein level in visceral fat and PPARγ and LPL protein level in skeletal muscle in the ECD group. Contrarily, a decrease in PPARγ mRNA level in skeletal muscle in the ECD group was observed. Therefore, we speculate that ECD regulates the lipid metabolic disorder by decreasing the blood lipid level. Moreover, the potential molecular mechanism of ECD is to promote the expression of PPARγ in visceral fat and skeletal muscle and the expression of LPL in skeletal muscle.

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Abstract 2834: A Short-Term High Fat Diet Impairs Cardiac High Energy Phosphate Metabolism, Exercise Capacity and Cognitive Function

Circulation ◽

10.1161/circ.118.suppl_18.s_784-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Cameron J Holloway ◽

Lindsay M Edwards ◽

Yaso Emmanuel ◽

Lowri Cochlin ◽

Damian J Tyler ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Cognitive Function ◽

Exercise Capacity ◽

High Fat Diet ◽

Calorie Intake ◽

High Fat ◽

Short Term ◽

Heart Failure Patients ◽

Plasma Ffas

Background: Heart failure patients have low cardiac phosphocreatine/ATP (PCr/ATP) ratios, abnormal exercise tolerance and impaired cognitive function, which may be related to elevated circulating free fatty acids (FFAs). We tested whether briefly raising plasma FFAs, using diet, causes abnormalities in heart, brain and skeletal muscle in healthy subjects Methods and Results: Healthy males (n = 16, age 22 ± 1 years), recruited from the University of Oxford, were randomised to five days of a high fat diet containing 75 ± 1% of calorie intake through fat consumption, or an isocaloric control diet, providing 23 ± 1% of calorie intake as fat. In a cross-over design, subjects undertook the alternate diet after a two week wash out period. Cardiac 31 P magnetic resonance (MR) spectroscopy and MR imaging, echocardiography, exhaustive cycling for 1 h, and CDR computerised cognitive tests were used to assess cardiac PCr/ATP, cardiac function, exercise capacity and cognitive function, respectively, before and after the diets. Subjects on the HFD had a two-fold elevation in plasma FFAs, 12% lower cardiac PCr/ATP with no change in cardiac function, and a 12% lower maximal exercise performance (see Figure ). They also had impaired attention and speed (2.2 vs. 1.9 s, p < 0.001, and 1.10 vs. 1.05 s, respectively, p < 0.01) Discussion: We have shown a short term, high fat diet raised plasma FFA concentrations, impaired myocardial energetics, exercise capacity and cognition. Therefore high plasma FFAs may be detrimental for heart, skeletal muscle and brain in normal subjects and suggests a potential mechanism of impairment in heart failure patients.

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L-Carnitine Is Involved in Hyperbaric Oxygen-Mediated Therapeutic Effects in High Fat Diet-Induced Lipid Metabolism Dysfunction

Molecules ◽

10.3390/molecules25010176 ◽

2020 ◽

Vol 25 (1) ◽

pp. 176 ◽

Cited By ~ 1

Author(s):

Junhua Yuan ◽

Qixiao Jiang ◽

Limin Song ◽

Yuan Liu ◽

Manwen Li ◽

...

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Lipid Metabolism ◽

Hyperbaric Oxygen ◽

High Fat Diet ◽

Therapeutic Effects ◽

Human Beings ◽

High Fat ◽

Adipose Tissues ◽

Expression Levels

Lipid metabolism dysfunction and obesity are serious health issues to human beings. The current study investigated the effects of hyperbaric oxygen (HBO) against high fat diet (HFD)-induced lipid metabolism dysfunction and the roles of L-carnitine. C57/B6 mice were fed with HFD or normal chew diet, with or without HBO treatment. Histopathological methods were used to assess the adipose tissues, serum free fatty acid (FFA) levels were assessed with enzymatic methods, and the endogenous circulation and skeletal muscle L-carnitine levels were assessed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, western blotting was used to assess the expression levels of PPARα, CPT1b, pHSL/HSL, and UCP1. HFD treatment increased body/adipose tissue weight, serum FFA levels, circulation L-carnitines and decreased skeletal muscle L-carnitine levels, while HBO treatment alleviated such changes. Moreover, HFD treatment increased fatty acid deposition in adipose tissues and decreased the expression of HSL, while HBO treatment alleviated such changes. Additionally, HFD treatment decreased the expression levels of PPARα and increased those of CPT1b in skeletal muscle, while HBO treatment effectively reverted such changes as well. In brown adipose tissues, HFD increased the expression of UCP1 and the phosphorylation of HSL, which was abolished by HBO treatment as well. In summary, HBO treatment may alleviate HFD-induced fatty acid metabolism dysfunction in C57/B6 mice, which seems to be associated with circulation and skeletal muscle L-carnitine levels and PPARα expression.

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Early skeletal muscle adaptations to short-term high-fat diet in humans before changes in insulin sensitivity

Obesity ◽

10.1002/oby.21031 ◽

2015 ◽

Vol 23 (4) ◽

pp. 720-724 ◽

Cited By ~ 19

Author(s):

Angela S. Anderson ◽

Kimberly R. Haynie ◽

Ryan P. McMillan ◽

Kristin L. Osterberg ◽

Nabil E. Boutagy ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

High Fat Diet ◽

High Fat ◽

Short Term ◽

Muscle Adaptations ◽

Skeletal Muscle Adaptations

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Short-term high-fat diet increases macrophage markers in skeletal muscle accompanied by impaired insulin signalling in healthy male subjects

Clinical Science ◽

10.1042/cs20140179 ◽

2014 ◽

Vol 128 (2) ◽

pp. 143-151 ◽

Cited By ~ 24

Author(s):

Mariëtte R. Boon ◽

Leontine E. H. Bakker ◽

Mariëlle C. Haks ◽

Edwin Quinten ◽

Gert Schaart ◽

...

Keyword(s):

Skeletal Muscle ◽

High Fat Diet ◽

Insulin Signalling ◽

Early Event ◽

Healthy Male ◽

High Fat ◽

Short Term ◽

Diet Induced Obesity ◽

Enhanced Expression ◽

Male Subjects

Short-term high-fat diet results in enhanced expression of markers for macrophages in skeletal muscle of healthy male subjects. This may be an early event in the development of insulin resistance in the course of high-fat diet induced obesity.

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