Glucose oversupply increases Δ9-desaturase expression and its metabolites in rat skeletal muscle

Houdali, B.; Wahl, Hans Günther; Kresi, M.; Nguyen, Von; Haap, Michael; Machicao, Fausto; Ammon, H. P. T.; Renn, W.; Schleicher, Erwin; Häring, Hans‐Ulrich

doi:10.1007/s00125-002-1015-2

Cited by 27 publications

(19 citation statements)

References 58 publications

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“…40). The expression of SCD1 but not SCD2 (36) is induced by a high-carbohydrate diet or glucose oversupply in skeletal muscle and in the heart (23,29,36). Glycolytic EDL muscles rely more on glucose supply for their main source of energy and have lower rates of FA oxidation and lower insulin sensitivity than SOL muscles (46,49).…”

Section: Discussionmentioning

confidence: 99%

The effect of dietary fat content on phospholipid fatty acid profile is muscle fiber type dependent

Janovská

Hatzinikolas

Mano

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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IR has been linked to alterations and increased saturation in the phospholipid composition of skeletal muscles. We aimed to determine whether HFD feeding affects fatty acid (FA) membrane profile in a muscle fiber type-specific manner. We measured phospholipid FAs and expression of FA synthesis genes in oxidative soleus (SOL) and glycolytic extensor digitorum longus (EDL) muscles from rats fed either standard chow (standard laboratory diet, SLD) or a HFD. The HFD increased fat mass, plasma insulin, and leptin levels. Compared with EDL, SOL muscles preferentially accumulated C18 over C16 FAs and n-6 over n-3 polyunsaturated FAs (PUFAs) on either diet. With the HFD, SOL muscles contained more n-9 monounsaturated FAs (MUFAs) and n-6 PUFAs and less n-7 MUFAs and n-3 PUFAs than EDL muscles and had lower unsaturation index, a pattern known to be associated with IR. Stearoyl-CoA desaturase-1 expression was ϳ13-fold greater in EDL than in SOL muscles but did not change with the HFD in either muscle. The expression of Elongase-5 was higher, and that of Elongase-6 (Elovl6) was lower in EDL compared with SOL muscles with both diets. In EDL muscles, the expression of Elovl6 was lower in the HFD than in the SLD. The pattern of FA uptake, expression, and diet-induced changes in FA desaturating and elongating enzymes maintained higher FA unsaturation in EDL muscles. Accordingly, the fiber type composition of skeletal muscles and their distribution may be important in the development and progression of obesity and IR. skeletal muscle; stearoyl-coenzyme A desaturase; elongases; obesity HIGH-FAT DIET (HFD) feeding leads to obesity in rodents as well as in humans (15, 17) and, in skeletal muscles, to an increase in the intracellular content of lipids and resistance to the actions of insulin (IR) and leptin.Skeletal muscle represents 40 -50% of the total body mass and is the major tissue responsible for whole body insulinstimulated glucose disposal. Skeletal muscle fibers are divided into three major categories, types I, IIa, and IIb. Type I fibers are slow-twitch, oxidative (SO) fibers with a high mitochondrial content; type IIa fibers are fast-twitch, oxidative-glycolytic (FOG) fibers that are high in both mitochondrial and glycogenolytic enzymes; type IIb fibers are fast-twitch, glycolytic (FG) fibers that are high in the enzymes of glycogenolysis (22,59). Although the oxidative muscle fibers are highly dependent on lipids as a substrate, the glycolytic or oxidativeglycolytic fibers utilize either predominantly glucose or a fuel mixture with an important contribution of glucose as a substrate under normal feeding conditions (46). Oxidative muscles are more insulin sensitive and have a greater insulin binding capacity (5), kinase activity of insulin receptor (25), content of glucose transporter (GLUT)4 (26), and insulin-stimulated glucose uptake (35) than glycolytic muscles. In obesity and IR, the distribution of fiber types is shifted from oxidative toward glycolytic muscle fibers (21).In skeletal muscle, saturated fatty acids (S...

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Section: Discussionmentioning

confidence: 99%

The effect of dietary fat content on phospholipid fatty acid profile is muscle fiber type dependent

Janovská

Hatzinikolas

Mano

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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“…Warensjo et al [23] found that SCD1 activity in serum cholesteryl esters under fasting conditions in humans predicted an increased risk of developing the metabolic syndrome. However, since this association was not independent of obesity and due to the fact that diets with a high amount of saturated fatty acids [36] and glucose [39] increased SCD1 activity, the authors of that report concluded that the observed relationships reflected compensatory upregulation of SCD1 activity to continuous intake of unhealthy diets [23]. Furthermore, in L6 myotubes SCD1 overproduction does not improve insulin signalling in basal conditions, but does protect from fatty acid-induced insulin resistance [40].…”

Section: Discussionmentioning

confidence: 99%

Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans

et al. 2008

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Aims/hypothesis Stearoyl-CoA desaturase 1 (SCD1) is the rate-limiting enzyme in monounsaturated fatty acid synthesis. It is imperative for the assembly of VLDL particles, which transport triacylglycerol (TG) from liver to adipose tissue and other sites. We aimed to determine the role of hepatic SCD1 activity in human glucose and lipid metabolism. Methods We studied 54 people participating in a lifestyle intervention programme with diet modification and increased physical activity. Insulin sensitivity was determined during a euglycaemic-hyperinsulinaemic clamp and estimated from an OGTT. Liver fat was quantified by 1 H-magnetic resonance spectroscopy at baseline and after 9 months of intervention. The pattern of fatty acids in serum VLDL-TGs was determined by ultracentrifugation followed by thin layer and gas chromatography, with the 18:1 n-9: 18:0 ratio providing an index of hepatic SCD1 activity. Results The hepatic SCD1 activity index correlated negatively with liver fat (r=−0.29, p=0.04) and positively with insulin sensitivity, both p=0.003) and clamp-derived (r=0.27, p=0.07). These correlations depended on overall adiposity. They were absent in leaner participants (n=27, liver fat: p=0.34, insulin sensitivity [OGTT]: p=0.75, insulin sensitivity [clamp]: p=0.24), but were strong in obese individuals (n=27, p=0.004, p=0.0002 and p=0.006, respectively). Furthermore, during intervention a high SCD1 activity index at baseline predicted a decrease in liver fat only in obese participants (r=−0.46, p=0.02). Conclusions/interpretation Our data suggest that high hepatic SCD1 activity may regulate fat accumulation in the liver and possibly protects from insulin resistance in obesity.

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“…A number of studies have examined the role of particular desaturase enzymes in diabetes and related disorders (6,7,14,21,23). The ⌬ 9 -desaturase enzyme converts saturated fatty acids to monounsaturated fatty acids.…”

Section: Discussionmentioning

confidence: 99%

“…Thus these enzymes are necessary for the biosynthesis of arachidonic acid, eicosapentaenoic acid, decosahexaenoic acid, and other unsaturated fatty acids (6,7). Insulin therapy reverses and overcorrects the diminished ⌬ 9 -and ⌬ 6 -desaturase activities and restores fatty acid composition to normal, except for the decrease in arachidonic acid (14). Thus alterations in fatty acid composition in tissues from diabetic animals reflect the consequences of insulin deficiency.…”

Section: Discussionmentioning

confidence: 99%

Distinct patterns of fat metabolism in skeletal muscle of normal-weight, overweight, and obese humans

Velan¹,

Said²,

Durst³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Velan SS, Said N, Durst C, Frisbee S, Frisbee J, Raylman RR, Thomas MA, Rajendran VM, Spencer RG, Alway SE. Distinct patterns of fat metabolism in skeletal muscle of normal-weight, overweight, and obese humans. Am J Physiol Regul Integr Comp Physiol 295: R1060 -R1065, 2008. First published July 30, 2008 doi:10.1152/ajpregu.90367.2008The link between body weight, lipid metabolism, and health risks is poorly understood and difficult to study. Magnetic resonance spectroscopy (MRS) permits noninvasive investigation of lipid metabolism. We extended existing two-dimensional MRS techniques to permit quantification of intra-and extramyocellular lipid (IMCL and EMCL, respectively) compartments and their degree of unsaturation in human subjects and correlated these results with body mass index (BMI). Using muscle creatine for normalization, we observed a statistically significant (P Ͻ 0.01) increase in the IMCL-to-creatine ratio with BMI (n ϭ 8 subjects per group): 5.9 Ϯ 1.7 at BMI Ͻ 25, 10.9 Ϯ 1.82 at 25 Ͻ BMI Ͻ 30, and 13.1 Ϯ 0.87 at BMI Ͼ 30. Similarly, the degree of IMCL unsaturation decreased significantly (P Ͻ 0.01) with BMI: 1.51 Ϯ 0.08 at BMI Ͻ 25, 1.30 Ϯ 0.11 at 25 Ͻ BMI Ͻ 30, and 0.90 Ϯ 0.14 at BMI Ͼ 30. We conclude that important aspects of lipid metabolism can be evaluated by two-dimensional MRS and propose that degree of unsaturation measured noninvasively may serve as a biomarker for lipid metabolic defects associated with obesity. magnetic resonance spectroscopy; lipid unsaturation; intramyocellular lipid; extramyocellular lipid THE AMOUNT OF BODY FAT is a risk factor for several obesityrelated disorders. Obesity is a known risk factor for the development of insulin resistance and diabetes and is a key component of metabolic syndrome. The causal relationship between increased dyslipidemia and adiposity and impaired glucose homeostasis is unclear, although it is known that lipid oversupply to the organs primarily involved in glucose homeostasis, that is, muscle, liver, and pancreas, leads to impaired insulin function in those tissues (22).Previous studies showed that intramyocellular lipid (IMCL) is increased with obesity and in non-insulin-dependent diabetes mellitus (9,11,15). It has been suggested that increased visceral adiposity and reduced lipid oxidation might contribute to the increase in IMCL (18). Thus the ability to monitor the IMCL pool and its properties noninvasively by magnetic resonance spectroscopy (MRS) has been an important development (4, 28). The correlation between the magnitude of the IMCL pool, as determined by MRS studies, and insulin resistance, diabetes, and disorders of lipid metabolism has been previously demonstrated (2,3,32,33). Nevertheless, quantification of IMCL and extramyocellular lipid (EMCL) by MRS remains highly problematic (32). The ability to distinguish IMCL from EMCL is based on their different bulk magnetic susceptibility effects due to their geometric arrangements within muscle, which leads to a spectroscopic frequency separation between the two pools; this sepa...

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Glucose oversupply increases Δ9-desaturase expression and its metabolites in rat skeletal muscle

Cited by 27 publications

References 58 publications

The effect of dietary fat content on phospholipid fatty acid profile is muscle fiber type dependent

The effect of dietary fat content on phospholipid fatty acid profile is muscle fiber type dependent

Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans

Distinct patterns of fat metabolism in skeletal muscle of normal-weight, overweight, and obese humans

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