scholarly journals One Week of Bed Rest Leads to Substantial Muscle Atrophy and Induces Whole-Body Insulin Resistance in the Absence of Skeletal Muscle Lipid Accumulation

Diabetes ◽  
2016 ◽  
Vol 65 (10) ◽  
pp. 2862-2875 ◽  
Author(s):  
Marlou L. Dirks ◽  
Benjamin T. Wall ◽  
Bas van de Valk ◽  
Tanya M. Holloway ◽  
Graham P. Holloway ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Lipid Accumulation ◽  
Bed Rest ◽  
Whole Body ◽  
Muscle Lipid ◽  
Skeletal Muscle Lipid

scholarly journals Rapid development of systemic insulin resistance with overeating is not accompanied by robust changes in skeletal muscle glucose and lipid metabolism

2013 ◽  
Vol 38 (5) ◽  
pp. 512-519 ◽  
Author(s):  
Andrea S. Cornford ◽  
Alexander Hinko ◽  
Rachael K. Nelson ◽  
Ariel L. Barkan ◽  
Jeffrey F. Horowitz
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Lipid Accumulation ◽  
Rapid Development ◽  
Insulin Response ◽  
Whole Body ◽  
Muscle Lipid ◽  
Wet Weight

Prolonged overeating and the resultant weight gain are clearly linked with the development of insulin resistance and other cardiometabolic abnormalities, but adaptations that occur after relatively short periods of overeating are not completely understood. The purpose of this study was to characterize metabolic adaptations that may accompany the development of insulin resistance after 2 weeks of overeating. Healthy, nonobese subjects (n = 9) were admitted to the hospital for 2 weeks, during which time they ate ∼4000 kcals·day−1 (70 kcal·kg−1 fat free mass·day−1). Insulin sensitivity was estimated during a meal tolerance test, and a muscle biopsy was obtained to assess muscle lipid accumulation and protein markers associated with insulin resistance, inflammation, and the regulation of lipid metabolism. Whole-body insulin sensitivity declined markedly after 2 weeks of overeating (Matsuda composite index: 8.3 ± 1.3 vs. 4.6 ± 0.7, p < 0.05). However, muscle markers of insulin resistance and inflammation (i.e., phosphorylation of IRS-1-Ser312, Akt-Ser473, and c-Jun N-terminal kinase) were not altered by overeating. Intramyocellular lipids tended to increase after 2 weeks of overeating (triacylglyceride: 7.6 ± 1.6 vs. 10.0 ± 1.8 nmol·mg−1 wet weight; diacylglyceride: 104 ± 10 vs. 142 ± 23 pmol·mg−1 wet weight) but these changes did not reach statistical significance. Overeating induced a 2-fold increase in 24-h insulin response (area under the curve (AUC); p < 0.05), with a resultant ∼35% reduction in 24-h plasma fatty acid AUC (p < 0.05). This chronic reduction in circulating fatty acids may help explain the lack of a robust increase in muscle lipid accumulation. In summary, our findings suggest alterations in skeletal muscle metabolism may not contribute meaningfully to the marked whole-body insulin resistance observed after 2 weeks of overeating.

Impaired Insulin Resistance in IF1-Deficient Mice Subjected to a High-Fat Diet with Reduced-Fat Mass and Skeletal Muscle Lipid Accumulation

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1748-P ◽  
Author(s):  
FENGYUAN HUANG ◽  
KEVIN YANG ◽  
KAMALAMMA SAJA ◽  
YICHENG HUANG ◽  
QINGQIANG LONG ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
High Fat ◽  
Muscle Lipid ◽  
Reduced Fat ◽  
Impaired Insulin ◽  
Skeletal Muscle Lipid ◽  
Deficient Mice

Intramyocellular fat storage in metabolic diseases

2016 ◽  
Vol 26 (1) ◽  
Author(s):  
Claire Laurens ◽  
Cedric Moro
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Metabolic Diseases ◽  
Recent Literature ◽  
Lipid Storage ◽  
Muscle Lipid ◽  
The Past ◽  
Skeletal Muscle Lipid ◽  
Ectopic Lipid Storage

AbstractOver the past decades, obesity and its metabolic co-morbidities such as type 2 diabetes (T2D) developed to reach an endemic scale. However, the mechanisms leading to the development of T2D are still poorly understood. One main predictor for T2D seems to be lipid accumulation in “non-adipose” tissues, best known as ectopic lipid storage. A growing body of data suggests that these lipids may play a role in impairing insulin action in metabolic tissues, such as liver and skeletal muscle. This review aims to discuss recent literature linking ectopic lipid storage and insulin resistance, with emphasis on lipid deposition in skeletal muscle. The link between skeletal muscle lipid content and insulin sensitivity, as well as the mechanisms of lipid-induced insulin resistance and potential therapeutic strategies to alleviate lipotoxic lipid pressure in skeletal muscle will be discussed.

SKELETAL MUSCLE LIPID CONTENT AND INSULIN RESISTANCE

2003 ◽  
Vol 35 (Supplement 1) ◽  
pp. S10
Author(s):  
C R. Bruce ◽  
M J. Anderson ◽  
A L. Carey ◽  
D G. Newman ◽  
A Bonen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Lipid Content ◽  
Muscle Lipid ◽  
Skeletal Muscle Lipid

scholarly journals Dietary Sphingomyelin Attenuates Adipose Inflammation and Skeletal Muscle Lipid Accumulation in C57BL/6J Mice Fed an Obesogenic Diet

2017 ◽  
Vol 31 ◽  
pp. 966.17-966.17
Author(s):  
Gregory H Norris ◽  
Christina Jiang ◽  
Caitlin M Porter ◽  
Courtney L. Millar ◽  
Christopher N Blesso
Keyword(s):  
Skeletal Muscle ◽  
Lipid Accumulation ◽  
Muscle Lipid ◽  
Skeletal Muscle Lipid ◽  
Obesogenic Diet ◽  
Adipose Inflammation

scholarly journals Mice lacking PKC-θ in skeletal muscle have reduced intramyocellular lipid accumulation and increased insulin responsiveness in skeletal muscle

2018 ◽  
Vol 314 (3) ◽  
pp. R468-R477 ◽  
Author(s):  
Bailey Peck ◽  
Josh Huot ◽  
Tim Renzi ◽  
Susan Arthur ◽  
Michael J. Turner ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Lipid Accumulation ◽  
Specific Effect ◽  
Whole Body ◽  
Mrna Levels ◽  
Intramyocellular Lipid ◽  
Fatty Acid Binding ◽  
Tissue Specific ◽  
Insulin Responsiveness

Protein kinase C-θ (PKC-θ) is a lipid-sensitive molecule associated with lipid-induced insulin resistance in skeletal muscle. Rodent models have not cohesively supported that PKC-θ impairs insulin responsiveness in skeletal muscle. The purpose of this study was to generate mice that lack PKC-θ in skeletal muscle and determine how lipid accumulation and insulin responsiveness are affected in that tissue. Mice lacking PKC-θ in skeletal muscle (SkMPKCθKO) and controls (SkMPKCθWT) were placed on a regular diet (RD) or high-fat diet (HFD) for 15 wk, followed by determination of food intake, fasting glucose levels, lipid accumulation, and insulin responsiveness. There were no differences between SkMPKCθWTand SkMPKCθKOmice on a RD. SkMPKCθKOmice on a HFD gained less weight from 10 through 15 wk of dietary intervention ( P < 0.05). This was likely due to less caloric consumption ( P = 0.0183) and fewer calories from fat ( P < 0.001) compared with SkMPKCθWTmice on a HFD. Intramyocellular lipid accumulation ( P < 0.0001), fatty acid binding protein 4, and TNF-α mRNA levels ( P < 0.05) were markedly reduced in SkMPKCθKOcompared with SkMPKCθWTmice on a HFD. As a result, fasting hyperglycemia was mitigated and insulin responsiveness, as indicated by Akt phosphorylation, was maintained in SkMPKCθKOon a HFD. Liver lipid accumulation was not affected by genotype, suggesting the deletion of PKC-θ from skeletal muscle has a tissue-specific effect. PKC-θ is a regulator of lipid-induced insulin resistance in skeletal muscle. However, the effects of this mutation may be tissue specific. Further work is warranted to comprehensively evaluated whole body metabolic responses in this model.

scholarly journals SUN-582 Effect of the Combination of Conjugated Estrogens and Bazedoxifene on Muscle and Serum Lipidome in Obese Postmenopausal Women: A Placebo-Controlled Randomized Pilot Trial

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Dragana Lovre ◽  
Kara Marlatt ◽  
Robbie A Beyl ◽  
Charles F Burant ◽  
Eric Ravussin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Postmenopausal Women ◽  
Lipid Accumulation ◽  
Pilot Trial ◽  
Density Lipoprotein ◽  
Low Density ◽  
Muscle Lipid ◽  
Lipid Species ◽  
Skeletal Muscle Lipid ◽  
Long Chain

Abstract Background and Objectives: Menopause is characterized by estrogen deficiency and predisposes women to weight gain and metabolic disturbances including lipid abnormalities. Orally-administered estrogens increase high-density lipoprotein (HDL) and triglycerides (TG) cholesterol and decreases low-density lipoprotein (LDL) cholesterol levels. The increase in serum TGs is not well understood. The objective of this study was to assess the effect of CE/BZA on serum and skeletal muscle lipid species in obese postmenopausal women. Methods: Randomized double-blind crossover pilot trial in 8 obese postmenopausal women (53± 3 years, BMI 35.7±3.2 kg/m2) assigned to 8 weeks of CE/BZA or placebo with 8 weeks washout in between. At the end of each 8-week treatment period, intrahepatic and skeletal muscle lipids were measured by proton magnetic resonance spectroscopy (1H-MRS) while serum and skeletal muscle lipidomics were assayed by ultrahigh performance liquid chromatography/mass spectrometry (UHPLC/MS). Results: No treatment differences were observed in intrahepatic lipid, soleus intramyocellular lipid (IMCL) or extramyocellular lipid (EMCL) as well as tibialis anterior IMCL or EMCL. The serum metabolome and lipidome comprised a total of 2002 biochemicals. Treatment with CE/BZA was associated with higher levels of diacylglycerols (DAGs) and triacylglycerols (TAGs) composed of long-chain saturated fatty acids (SFA, palmitic C16:0 and arachidic C20:0), monounsaturated FAs (MUFA, palmitoleic C16:1, oleic C18:1 and ecosenoic C20:1), and polyunsaturated FAs (PUFA, linoleic C18:2, arachidonic C20:4, eicosapentaenoic C20:5, and docosahexaenoic C22:6) compared to placebo (all p&lt;0.05). Treatment with CE/BZA was also associated with lower levels of several acylcarnitine species, which are markers of FA oxidation, including long-chain SFA (C14, C16 and C18), MUFA (C18:1 and C24:1) and PUFA (C18:2, C20:2 and C20:4). In addition, treatment with CE/BZA was associated with higher levels of phosphatidylcholines (PCs), phosphatidylinositols (PIs), phosphatidylethanolamines (PEs), sphingomyelins (SMs), and ceramides (CER), as well as lower levels of lysophophatidylcholines (LPCs). There were no treatment differences in carnitine or ketones levels. The skeletal muscle analysis comprised a total of 652 biochemicals, but unlike in serum, no significant treatment differences were observed in the skeletal muscle lipidome. Conclusions: Our lipidomic analysis supports a model in which CE/BZA (and likely all oral estrogens) increases hepatic de novo FA synthesis and esterification into TAGs for export into TAG-rich very low-density lipoproteins, as well as decreased FA oxidation, respectively. Although CE/BZA treatment inhibits FA oxidation, it is not associated with hepatic lipid accumulation as measured by MRS, or skeletal muscle lipid accumulation measured by MRS and lipidomics.

scholarly journals Skeletal Muscle Lipid Peroxidation and Insulin Resistance in Humans

2012 ◽  
Vol 97 (7) ◽  
pp. E1182-E1186 ◽  
Author(s):  
Katherine H. Ingram ◽  
Helliner Hill ◽  
Douglas R. Moellering ◽  
Bradford G. Hill ◽  
Cristina Lara-Castro ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Lipid Peroxidation ◽  
Insulin Sensitivity ◽  
Waist Circumference ◽  
Muscle Protein ◽  
Protein Carbonyls ◽  
Protein Carbonyl Content ◽  
Muscle Lipid ◽  
Skeletal Muscle Lipid

Abstract Objective: The relationships among skeletal muscle lipid peroxidation, intramyocellular lipid content (IMCL), and insulin sensitivity were evaluated in nine insulin-sensitive (IS), 13 insulin-resistant (IR), and 10 adults with type 2 diabetes (T2DM). Design: Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp [glucose disposal rate (GDR)]. Lipid peroxidation was assessed by 4-hydroxynonenal (HNE)-protein adducts and general oxidative stress by protein carbonyl content. All patients were sedentary. Results: Protein-HNE adducts were elevated 1.6-fold in T2DM compared with IS adults, whereas IR showed intermediate levels of HNE-modified proteins. Protein-HNE adducts correlated with GDR, waist circumference, and body mass index. IMCL was increased by 4.0- and 1.9-fold in T2DM and IR patients, respectively, compared with IS, and was correlated with GDR and waist circumference but not BMI. Protein carbonyls were not different among groups and did not correlate with any of the measured variables. Correlations were detected between IMCL and protein-HNE. Conclusion: Our data show for the first time that skeletal muscle protein-HNE adducts are related to the severity of insulin resistance in sedentary adults. These results suggest that muscle lipid peroxidation could be involved in the development of insulin resistance.

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