Dataset Information

Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity.

ABSTRACT:

Aims/hypothesis

Mitochondria operate in networks, adapting to external stresses and changes in cellular metabolic demand and are subject to various quality control mechanisms. On the basis of these traits, we here hypothesise that the regulation of mitochondrial networks in skeletal muscle is hampered in humans with compromised oxidative capacity and insulin sensitivity.

Methods

In a cross-sectional design, we compared four groups of participants (selected from previous studies) ranging in aerobic capacity and insulin sensitivity, i.e. participants with type 2 diabetes (n?=?11), obese participants without diabetes (n?=?12), lean individuals (n?=?10) and endurance-trained athletes (n?=?12); basal, overnight fasted muscle biopsies were newly analysed for the current study and we compared the levels of essential mitochondrial dynamics and quality control regulatory proteins in skeletal muscle tissue.

Results

Type 2 diabetes patients and obese participants were older than lean participants and athletes (58.6?±?4.0 and 56.7?±?7.2 vs 21.8?±?2.5 and 25.1?±?4.3 years, p?2, p?Conclusions/interpretationCollectively, our data suggest that mitochondrial dynamics and quality control in skeletal muscle are linked to oxidative capacity in humans, which may play a role in the maintenance of muscle insulin sensitivity. CLINICAL TRIAL REGISTRY: numbers NCT00943059, NCT01298375 and NL1888 Graphical abstract.

SUBMITTER: Houzelle A

PROVIDER: S-EPMC7801361 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity.

Houzelle Alexandre A Jörgensen Johanna A JA Schaart Gert G Daemen Sabine S van Polanen Nynke N Fealy Ciarán E CE Hesselink Matthijs K C MKC Schrauwen Patrick P Hoeks Joris J

Diabetologia 20201130 2

<h4>Aims/hypothesis</h4>Mitochondria operate in networks, adapting to external stresses and changes in cellular metabolic demand and are subject to various quality control mechanisms. On the basis of these traits, we here hypothesise that the regulation of mitochondrial networks in skeletal muscle is hampered in humans with compromised oxidative capacity and insulin sensitivity.<h4>Methods</h4>In a cross-sectional design, we compared four groups of participants (selected from previous studies) r ...[more]

PMID: 33258025

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Project description:Accumulation of diacylglycerol (DAG) and sphingolipids is thought to promote skeletal muscle insulin resistance by altering cellular signaling specific to their location. However,the subcellular localization of bioactive lipids in human skeletal muscle is largely unknown. We evaluated subcellular localization of skeletal muscle DAGs and sphingolipids in lean individuals (n = 15), endurance-trained athletes (n = 16), and obese men and women with (n = 12) and without type 2 diabetes (n = 15). Muscle biopsies were fractionated into sarcolemmal, cytosolic, mitochondrial/ER, and nuclear compartments. Lipids were measured using liquid chromatography tandem mass spectrometry, and insulin sensitivity was measured using hyperinsulinemic-euglycemic clamp. Sarcolemmal 1,2-DAGs were not significantly related to insulin sensitivity. Sarcolemmal ceramides were inversely related to insulin sensitivity, with a significant relationship found for the C18:0 species. Sarcolemmal sphingomyelins were also inversely related to insulin sensitivity, with the strongest relationships found for the C18:1, C18:0, and C18:2 species. In the mitochondrial/ER and nuclear fractions, 1,2-DAGs were positively related to, while ceramides were inversely related to, insulin sensitivity. Cytosolic lipids as well as 1,3-DAG, dihydroceramides, and glucosylceramides in any compartment were not related to insulin sensitivity. All sphingolipids but only specific DAGs administered to isolated mitochondria decreased mitochondrial state 3 respiration. These data reveal previously unknown differences in subcellular localization of skeletal muscle DAGs and sphingolipids that relate to whole-body insulin sensitivity and mitochondrial function in humans. These data suggest that whole-cell concentrations of lipids obscure meaningful differences in compartmentalization and suggest that subcellular localization of lipids should be considered when developing therapeutic interventions to treat insulin resistance. National Institutes of Health General Clinical Research Center (RR-00036), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01DK089170), NIDDK (T32 DK07658), and Colorado Nutrition Obesity Research Center (P30DK048520).

Dataset Information

Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity.

Aims/hypothesis

Methods

Results

Publications

Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity.

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