Long- and Medium-Chain Fatty Acids Induce Insulin Resistance to a Similar Extent in Humans Despite Marked Differences in Muscle Fat Accumulation

Hoeks, Joris; Mensink, Marco; Hesselink, Matthijs K. C.; Ekroos, Kim; Schrauwen, Patrick

doi:10.1210/jc.2011-1884

Cited by 29 publications

(20 citation statements)

References 41 publications

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“…It has been reported (103,149) that MCFAs, in contrast to LCFAs, contribute to maintain a high sensitivity of muscle cells to insulin. This view has, however, not been confirmed by other authors (150). It is also worthy to note that CoA esters of SCFAs and MCFAs accumulate in tissues in various pathological situations, such as the Reye syndrome (151).…”

Section: Generation Of Reactive Oxygen Speciesmentioning

confidence: 77%

Short- and medium-chain fatty acids in energy metabolism: the cellular perspective

Schönfeld

Wojtczak

2016

Journal of Lipid Research

760

523

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Section: Generation Of Reactive Oxygen Speciesmentioning

confidence: 77%

Short- and medium-chain fatty acids in energy metabolism: the cellular perspective

Schönfeld

Wojtczak

2016

Journal of Lipid Research

760

523

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“…Typically, this results in elevated plasma FFA levels up to the millimolar range (compared with 200-300 μmol under control conditions). These studies have robustly and consistently shown that infusion of lipid emulsions results in a significant increase in IMCL content (Bachmann et al, 2001;Brechtel et al, 2001a;Brehm et al, 2010;Hoeks et al, 2012;Lee et al, 2013) in the type I and type II muscle fibers of healthy male individuals and highly trained athletes (Phielix et al, 2012). In these lipid emulsion infusion studies, the increase in IMCL content was paralleled by a decrease in insulin-stimulated glucose uptake in muscle.…”

Section: High-fat Diet and Lipid Infusionmentioning

confidence: 83%

The effect of diet and exercise on lipid droplet dynamics in human muscle tissue

Daemen

Polanen

Hesselink

2018

Journal of Experimental Biology

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The majority of fat in the human body is stored as triacylglycerols in white adipose tissue. In the obese state, adipose tissue mass expands and excess lipids are stored in non-adipose tissues, such as skeletal muscle. Lipids are stored in skeletal muscle in the form of small lipid droplets. Although originally viewed as dull organelles that simply store lipids as a consequence of lipid overflow from adipose tissue, lipid droplets are now recognized as key components in the cell that exert a variety of relevant functions in multiple tissues (including muscle). Here, we review the effect of diet and exercise interventions on myocellular lipid droplets and their putative role in insulin sensitivity from a human perspective. We also provide an overview of lipid droplet biology and identify gaps for future research.

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“…This literature, however, remains mixed as training has also been shown to be associated with higher total DAG (1), no change in total DAG (17), and no change in total ceramides (1,17). The use of lipid plus heparin to significantly increase FFA two-to fourfold above baseline in sedentary participants does not alter muscle DAG (as measured by DAG-kinase assay) (45) or ceramide content (25,45). Our findings extend this literature by using serial biopsies to examine how training modifies muscle lipid accumulation, as measured by liquid chromatography/tandem mass spectrometry, in response to a more modest FFA exposure.…”

Section: Discussionmentioning

confidence: 99%

Training status diverges muscle diacylglycerol accumulation during free fatty acid elevation

Chow

Mashek

Austin

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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How endurance training alters muscle lipid metabolism while preserving insulin sensitivity remains unclear. Because acute free fatty acid (FFA) elevation by lipid infusion reduces insulin sensitivity, we hypothesized that training status would alter accumulation of muscle triacylglycerol (TAG), diacylglycerol (DAG), ceramide, and acylcarnitine during acute FFA elevation. Trained (n ϭ 15) and sedentary (n ϭ 13) participants matched for age, sex, and BMI received either a 6-h infusion of lipid (20% Intralipid at 90 ml/h) or glycerol (2.25 g/100 ml at 90 ml/h) during a hyperinsulinemic euglycemic clamp. Muscle biopsies were taken at 0, 120, and 360 min after infusion initiation to measure intramyocellular concentrations of TAG, DAG, ceramides, and acylcarnitines by liquid chromatography-tandem mass spectrometry. Trained participants had a higher V O2 max and insulin sensitivity than sedentary participants. The lipid infusion produced a comparable elevation of FFA (594 Ϯ 90 mol/l in trained, 721 Ϯ 30 mol/l in sedentary, P ϭ 0.4) and a decline in insulin sensitivity (Ϫ44.7% trained vs. Ϫ47.2% sedentary, P ϭ 0.89). In both groups, lipid infusion increased the linoleic and linolenic acid content of TAG without changing total TAG. In the sedentary group, lipid infusion increased total, oleic, and linoleic acid and linolenic acid content of DAG. Regardless of training status, lipid infusion did not alter total ceramide, saturated ceramide, palmitoyl-carnitine, or oleoyl-carnitine. We conclude that during acute FFA elevation, trained adults have a similar decline in insulin sensitivity with less accumulation of muscle DAG than sedentary adults, suggesting that lipid-induced insulin resistance can occur without elevation of total muscle DAG.training; intramyocellular lipid; diacylglycerol; insulin sensitivity; free fatty acids INSULIN RESISTANCE IS A CRITICAL CONTRIBUTOR to type 2 diabetes mellitus (T2DM), a disease that adversely affects millions of Americans. Insulin resistance has a well-established association with the metabolic syndrome (15) and predates T2DM (32). Because skeletal muscle is the largest site of insulin resistance (16,43), there is intense interest in understanding the mechanism of insulin resistance in these tissues.In sedentary humans, muscle insulin resistance has been attributed to lipotoxicity, which is defined as the elevation of lipids and/or lipid metabolites within blood or tissues with subsequent metabolic derangement. Several lines of evidence support this theory. Despite hyperinsulinemia, free fatty acid (FFA) levels are roughly two times higher in humans with obesity (2), insulin resistance (2), or T2DM (39) than in healthy humans. FFA elevation, in turn, increases intramyocellular lipid (IMCL) levels (10), a measurement that in sedentary humans is inversely associated with insulin sensitivity (30, 35). Although FFA elevation was initially thought to increase muscle insulin resistance by increasing IMCL (10), subsequent work has suggested that lipid metabolites such as diacylglycerol (DAG)...

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Long- and Medium-Chain Fatty Acids Induce Insulin Resistance to a Similar Extent in Humans Despite Marked Differences in Muscle Fat Accumulation

Abstract: Although we confirm that MCFA do not lead to ceramide and IMTG accumulation in skeletal muscle tissue in humans, they do induce insulin resistance. These results indicate that, in humans, MCFA may not be beneficial in preventing peripheral insulin resistance.

Cited by 29 publications

References 41 publications

Short- and medium-chain fatty acids in energy metabolism: the cellular perspective

Short- and medium-chain fatty acids in energy metabolism: the cellular perspective

The effect of diet and exercise on lipid droplet dynamics in human muscle tissue

Training status diverges muscle diacylglycerol accumulation during free fatty acid elevation

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