Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects.

Jacob, Stephan; Machann, Jürgen; Rett, K.; Brechtel, Klaus; Volk, A.; Renn, W.; Maerker, Elke; Matthaei, S.; Schick, Fritz; Claussen, Claus D.; Häring, Hans Ulrich

doi:10.2337/diabetes.48.5.1113

Cited by 566 publications

(486 citation statements)

References 16 publications

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“…The observation of increased IMCL in insulin-resistant subjects (10)(11)(12)(13)(14) supported the hypothesis of a possible role of IMCL in the pathogenesis of skeletal muscle insulin resistance and type 2 diabetes mellitus. The possibility of studying this important relation noninvasively and with high accuracy [coefficient of variation as low as about 6% (2)] boosted interest in 1 H-MRS studies on IMCL and the number of succeeding publications considerably (15)(16)(17)(18)(19).…”

Section: Relation Between Imcl Content and Insulin Sensitivitysupporting

confidence: 56%

“…the higher the IMCL content, the lower the glucose metabolic clearance rate (12). Several other studies also showed an association between IMCL accumulation and insulin resistance; however, there were also contradictory details: Krššák et al studied a group of normal-weight nondiabetic adults without family history of diabetes and found significant negative correlation between IMCL of soleus muscle and insulin sensitivity, but no relation between IMCL and BMI, age and fasting plasma concentrations of triglycerides (13).…”

Section: Relation Between Imcl Content and Insulin Sensitivitymentioning

confidence: 99%

“…In other words, the content of EMCL in a spectrum is at least as much an indicator of the care that has been taken in the positioning of the voxel as it is determined by the obesity of the individual. and insulin sensitivity are related (10)(11)(12)(13)(14). Besides this important crosslink, Fig.…”

Section: Introductionmentioning

confidence: 99%

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Role of proton MR for the study of muscle lipid metabolism

et al. 2006

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1 H-MR spectroscopy (MRS) of intramyocellular lipids (IMCL) became particularly important when it was recognized that IMCL levels are related to insulin sensitivity. While this relation is rather complex and depends on the training status of the subjects, various other influences such as exercise and diet also influence IMCL concentrations. This may open insight into many metabolic interactions; however, it also requires careful planning of studies in order to control all these confounding influences. This review summarizes various historical, methodological, and practical aspects of 1 H-MR spectroscopy (MRS) of muscular lipids. That includes a differentiation of bulk magnetic susceptibility effects and residual dipolar coupling that can both be observed in MRS of skeletal muscle, yet affecting different metabolites in a specific way. Fitting of the intra-(IMCL) and extramyocellular (EMCL) signals with complex line shapes and the transformation into absolute concentrations is discussed. Since the determination of IMCL in muscle groups with oblique fiber orientation or in obese subjects is still difficult, potential improvement with high-resolution spectroscopic imaging or at higher field strength is considered. Fat selective imaging is presented as a possible alternative to MRS and the potential of multinuclear MRS is discussed. 1 H-MRS of muscle lipids allows non-invasive and repeated studies of muscle metabolism that lead to highly relevant findings in clinics and patho-physiology.

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Section: Relation Between Imcl Content and Insulin Sensitivitysupporting

confidence: 56%

Section: Relation Between Imcl Content and Insulin Sensitivitymentioning

confidence: 99%

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Role of proton MR for the study of muscle lipid metabolism

et al. 2006

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“…7,19,20 The role of IMCL in diabetes is not fully understood, however, an inverse correlation of IMCL levels and insulin sensitivity has been observed by several groups. [21][22][23][24] Figure 3. Orientation dependence of the 1 H-MR spectrum of human muscle.…”

Section: Susceptibility Effects: Separation Of Imcl and Emclmentioning

confidence: 99%

Dipolar coupling and ordering effects observed in magnetic resonance spectra of skeletal muscle

Boesch

Kreis

2001

NMR in Biomedicine

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Skeletal muscle is a biological structure with a high degree of organization at different spatial levels. This order influences magnetic resonance (MR) in vivo-in particular 1 H-spectra-by a series of effects that have very distinct physical sources and biomedical applications: (a) bulk fat (extramyocellular lipids, EMCL) along fasciae forms macroscopic plates, changing the susceptibility within these structures compared to the spherical droplets that contain intra-myocellular lipids (IMCL); this effect leads to a separation of the signals from EMCL and IMCL; (b) dipolar coupling effects due to anisotropic motional averaging have been shown for 1 H-resonances of creatine, taurine, and lactate; (c) aromatic protons of carnosine show orientation-dependent effects that can be explained by dipolar coupling, chemical shift anisotropy or by relaxation anisotropy; (d) limited rotational freedom and/or compartmentation may explain differences of 1 H-MR-visibility of the creatine/phosphocreatine resonances; (e) lactate 1 H-MR resonances are reported to reveal information on tissue compartmentation; (f) transverse relaxation of water and metabolites show multiple components, indicative of intra-, extracellular and/or macromolecular-bound pools, and in addition dipolar or J-coupling lead to a modulation of the signal decay, hindering straightforward interpretation; (g) diffusion weighted 31 P-MRS has shown restricted diffusion of phosphocreatine; (h) magnetization transfer (MT) indicates that there is a motionally restricted proton pool in spin-exchange with free creatine; reduced availability or restricted motion of creatine is particularly important for an estimation of ADP from 31 P-MR spectra, and in addition MT effects may alter the signal intensity of creatine 1 H-resonances following water-suppression pulses; (i) transcytolemmal water-exchange can be studied in 1 H-MRS by contrast-agents applied to the extracellular space; (k) transport of glucose across the cell membrane has been studied in diabetes patients using a combination of 13 C-and 31 P-MRS; and (l) residual quadrupolar interaction in 23 Na MR spectra from human skeletal muscle suggest that sodium ions are bound to ordered muscular structures.

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“…Numerous studies have reported the association between elevated plasma NEFA concentrations, intramyocellular triacylglycerol (IMTG, often also abbreviated to IMCL) accumulation and the development of insulin resistance and/or type 2 diabetes [1][2][3][4][5][6][7]. The Randle (glucose-fatty acid) cycle has often been used to explain the mechanism behind skeletal muscle insulin resistance induced by fatty acid (FA) [8].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2005

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Aims/hypothesis: In the present study, we investigated the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use in type 2 diabetic patients. Materials and methods: We studied ten type 2 diabetic patients under the following conditions:(1) at rest; (2) during 60 min of cycling exercise at 50% of maximal workload capacity and subsequent recovery. Studies were done under normal, fasting conditions (control trial: CON) and following administration of a nicotinic acid analogue (low plasma non-esterified fatty acid trial: LFA). Continuous [U-13 C]palmitate and [6,6 -2 H 2 ]glucose infusions were applied to quantify plasma NEFA and glucose oxidation rates, and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in lipid and glycogen content specific to muscle fibre type. Results: Following administration of the nicotinic acid analogue (Acipimox), the plasma NEFA rate of appearance was effectively reduced, resulting in lower NEFA concentrations in the LFA trial (p<0.001). Plasma NEFA oxidation rates were substantially reduced at rest, during exercise and subsequent recovery in the LFA trial.The lower plasma NEFA oxidation rates were compensated by an increase in IMTG and endogenous carbohydrate use (p<0.05). Plasma glucose disposal rates did not differ between trials. In accordance with the tracer data, a greater net decline in type I muscle fibre lipid content was observed following exercise in the LFA trial (p<0.05). Conclusions/interpretation: This study shows that plasma NEFA availability regulates IMTG use, and that adipose tissue lipolytic inhibition, in combination with exercise, could be an effective means of augmenting intramuscular lipid and glycogen use in type 2 diabetic patients in an overnight fasted state.

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Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects.

Cited by 566 publications

References 16 publications

Role of proton MR for the study of muscle lipid metabolism

Role of proton MR for the study of muscle lipid metabolism

Dipolar coupling and ordering effects observed in magnetic resonance spectra of skeletal muscle

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

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