Intramyocellular lipid content in type 2 diabetes patients compared with overweight sedentary men and highly trained endurance athletes

Abstract

Recent evidence suggests that intramyocellular lipid (IMCL) accretion is associated with obesity and the development of insulin resistance and/or type 2 diabetes. However, trained endurance athletes are markedly insulin sensitive, despite an elevated mixed muscle lipid content. In an effort to explain this metabolic paradox, we compared muscle fiber type-specific IMCL storage between populations known to have elevated IMCL deposits. Immunofluorescence microscopy was performed on muscle biopsies obtained from eight highly trained endurance athletes, eight type 2 diabetes patients, and eight overweight, sedentary men after an overnight fast. Mixed muscle lipid content was substantially greater in the endurance athletes (4.0 +/- 0.4% area lipid stained) compared with the diabetes patients and the overweight men (2.3 +/- 0.4 and 2.2 +/- 0.5%, respectively). More than 40% of the greater mixed muscle lipid content was attributed to a higher proportion type I muscle fibers (62 +/- 8 vs. 38 +/- 3 and 33 +/- 7%, respectively), which contained 2.8 +/- 0.3-fold more lipid than the type II fibers. The remaining difference was explained by a significantly greater IMCL content in the type I muscle fibers of the trained athletes. Differences in IMCL content between groups or fiber types were accounted for by differences in lipid droplet density, not lipid droplet size. IMCL distribution showed an exponential increase in lipid content from the central region toward the sarcolemma, which was similar between groups and fiber types. In conclusion, IMCL contents can be substantially greater in trained endurance athletes compared with overweight and/or type 2 diabetes patients. Because structural characteristics and intramyocellular distribution of lipid aggregates seem to be similar between groups, we conclude that elevated IMCL deposits are unlikely to be directly responsible for inducing insulin resistance.

Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients

“…As elevated IMTG accretion in type 2 diabetic patients is the result of a structural imbalance between NEFA uptake, IMTG deposition and its subsequent mobilisation and/or oxidation [21][22][23], it has been suggested that an elevated IMTG turnover rate can prevent excessive accumulation of intramyocellular FA metabolites [9, 10, 13-16, 44, 45] and/or reduce the degree of intramyocellular lipid peroxidation [17]. In agreement, interventions known to Fig.…”

“…Multiple serial sections (5 μm) were thaw-mounted together on uncoated, pre-cleaned glass slides for each subject. To determine muscle fibre type specific IMTG content, cross-sections were stained with oil red O together with immunolabelled cellular constituents using a previously described protocol [23,25,41]. For each muscle biopsy, a total of 84±4 muscle fibres were analysed for lipid content.…”

“…Recent data indicate that this imbalance, and not the actual size or intramyocellular distribution of the IMTG pool, is responsible for the development of skeletal muscle insulin resistance [21][22][23]. It has been speculated that an elevated IMTG utilisation rate will prevent excess accumulation of intramyocellular TG and/or FA (metabolites).…”

Substrate source utilisation in long-term diagnosed type 2 diabetes patients at rest, and during exercise and subsequent recovery

“…Multiple serial sections (5 μm) were thaw-mounted together on uncoated, precleaned glass slides for each subject. To determine muscle fibre type-specific IMTG content, cross-sections were stained with Oil red O together with immunolabelled cellular constituents using a protocol described before [2]. For each muscle biopsy a total of 58±7 and 49±4 muscle fibres were analysed for lipid content for diabetes patients and control subjects respectively.…”

“…Disturbances in fatty acid metabolism, as found in sedentary, obese and/or type 2 diabetes patients, are an important factor in the development of skeletal muscle insulin resistance [1][2][3]. Elevated fatty acid delivery and/or impaired fatty acid oxidation result in net intramyocellular accumulation of triacylglycerol and fatty acid metabolites (such as fatty acyl-CoA, ceramides and diacylglycerol).…”