Dietary enrichment with fish oil prevents high fat-induced metabolic dysfunction in skeletal muscle in mice.

High saturated fat (HF-S) diets increase intramyocellular lipid, an effect ameliorated by omega-3 fatty acids in vitro and in vivo, though little is known about sex- and muscle fiber type-specific effects. We compared effects of standard chow, HF-S, and 7.5% HF-S replaced with fish oil (HF-FO) diets on the metabolic profile and lipid metabolism gene and protein content in red (soleus) and white (extensor digitorum longus) muscles of male and female C57BL/6 mice (n = 9-12/group). Weight gain was similar in HF-S- and HF-FO-fed groups. HF-S feeding increased mesenteric fat mass and lipid marker, Oil Red O, in red and mixed muscle; HF-FO increased interscapular brown fat mass. Compared to chow, HF-S and HF-FO increased expression of genes regulating triacylglycerol synthesis and fatty acid transport, HF-S suppressed genes and proteins regulating fatty acid oxidation, whereas HF-FO increased oxidative genes, proteins and enzymes and lipolytic gene content, whilst suppressing lipogenic genes. In comparison to HF-S, HF-FO further increased fat transporters, markers of fatty acid oxidation and mitochondrial content, and reduced lipogenic genes. No diet-by-sex interactions were observed. Neither diet influenced fiber type composition. However, some interactions between muscle type and diet were observed. HF-S induced changes in triacylglycerol synthesis and lipogenic genes in red, but not white, muscle, and mitochondrial biogenesis and oxidative genes were suppressed by HF-S and increased by HF-FO in red muscle only. In conclusion, HF-S feeding promotes lipid storage in red muscle, an effect abrogated by the fish oil, which increases mediators of lipolysis, oxidation and thermogenesis while inhibiting lipogenic genes. Greater storage and synthesis, and lower oxidative genes in red, but not white, muscle likely contribute to lipid accretion encountered in red muscle. Despite several gender-dimorphic genes, both sexes exhibited a similar HF-S-induced metabolic and gene expression profile; likewise fish oil was similarly protective in both sexes.

The use of adipose tissue-conditioned media to demonstrate the differential effects of fat depots on insulin-stimulated glucose uptake in a skeletal muscle cell line.

SUMMARY: We aimed to study the depot-specific effect of adipose tissue on insulin sensitivity of skeletal muscle in vitro. Adipose tissue-conditioned medium (CM) was generated from visceral and subcutaneous fat from obese subjects. CM from visceral as compared to subcutaneous fat had higher concentrations of interleukin (IL)-6 (15-fold; P < 0.05) and IL-8 (8-fold; P < 0.05). CM from visceral fat (1:128 dilution) reduced insulin-stimulated glucose uptake in L6 myotubes by 19% (P < 0.05), an effect mediated by a nuclear factor kappa B (NFκB)/mammalian target of rapamycin complex 1 (mTORC1)-dependent pathway and partially reversed by neutralizing IL-6. IL-6 at a concentration comparable to that in CM from visceral fat reduced insulin-stimulated glucose uptake by 53% (P < 0.05), an effect abolished by inhibiting NFκB or mTORC1. We demonstrated the utility of the CM-myotube system and identified IL-6 as a major cytokine mediating visceral fat-induced muscle insulin resistance.:

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

A high-saturated-fat diet (HFD) induces obesity and insulin resistance (IR). 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 approximately 13-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.

The expression of receptors for endocannabinoids in human and rodent skeletal muscle.

The endocannabinoid system is a lipid derived signalling system that has been shown to regulate appetite and energy metabolism. The most abundant endogenous endocannabinoid, anandamide, has been shown to activate the cannabinoid receptor type 1 (CB1) and type 2 (CB2) as well as the 'non-cannabinoid' transient receptor potential channel-vanilloid sub-family member 1 (TRPV1), before being rapidly metabolised by fatty acid amide hydrolase (FAAH). We have previously demonstrated the expression of CB1 and studied the effects of CB1 activation and inhibition in human skeletal muscle myotubes, however, not all results could be explained by CB1 mediated effects. This suggests that other receptors which are activated by endocannabinoids may be present in skeletal muscle. In this study we describe the presence of not only CB1, but also CB2, TRPV1 and the degrading enzyme FAAH in human and rodent skeletal muscle using reverse transcription polymerase chain reaction (RT-PCR).