mRNA expression of genes involved in fatty acid utilization in skeletal muscle and white adipose tissues of sows during lactation

O-1602 and O-1918 are atypical cannabinoid ligands for GPR55 and GPR18, which may be novel pharmaceuticals for the treatment of obesity by targeting energy homeostasis regulation in skeletal muscle. This study aimed to determine the effect of O-1602 or O-1918 on markers of oxidative capacity and fatty acid metabolism in the skeletal muscle. Diet-induced obese (DIO) male Sprague Dawley rats were administered a daily intraperitoneal injection of O-1602, O-1918 or vehicle for 6 weeks. C2C12 myotubes were treated with O-1602 or O-1918 and human primary myotubes were treated with O-1918. GPR18 mRNA was expressed in the skeletal muscle of DIO rats and was up-regulated in red gastrocnemius when compared with white gastrocnemius. O-1602 had no effect on mRNA expression on selected markers for oxidative capacity, fatty acid metabolism or adiponectin signalling in gastrocnemius from DIO rats or in C2C12 myotubes, while APPL2 mRNA was up-regulated in white gastrocnemius in DIO rats treated with O-1918. In C2C12 myotubes treated with O-1918, PGC1α, NFATc1 and PDK4 mRNA were up-regulated. There were no effects of O-1918 on mRNA expression in human primary myotubes derived from obese and obese T2DM individuals. In conclusion, O-1602 does not alter mRNA expression of key pathways important for skeletal muscle energy homeostasis in obesity. In contrast, O-1918 appears to alter markers of oxidative capacity and fatty acid metabolism in C2C12 myotubes only. GPR18 is expressed in DIO rat skeletal muscle and future work could focus on selectively modulating GPR18 in a tissue-specific manner, which may be beneficial for obesity-targeted therapies.

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L-Carnitine Is Involved in Hyperbaric Oxygen-Mediated Therapeutic Effects in High Fat Diet-Induced Lipid Metabolism Dysfunction

Molecules ◽

10.3390/molecules25010176 ◽

2020 ◽

Vol 25 (1) ◽

pp. 176 ◽

Cited By ~ 1

Author(s):

Junhua Yuan ◽

Qixiao Jiang ◽

Limin Song ◽

Yuan Liu ◽

Manwen Li ◽

...

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Lipid Metabolism ◽

Hyperbaric Oxygen ◽

High Fat Diet ◽

Therapeutic Effects ◽

Human Beings ◽

High Fat ◽

Adipose Tissues ◽

Expression Levels

Lipid metabolism dysfunction and obesity are serious health issues to human beings. The current study investigated the effects of hyperbaric oxygen (HBO) against high fat diet (HFD)-induced lipid metabolism dysfunction and the roles of L-carnitine. C57/B6 mice were fed with HFD or normal chew diet, with or without HBO treatment. Histopathological methods were used to assess the adipose tissues, serum free fatty acid (FFA) levels were assessed with enzymatic methods, and the endogenous circulation and skeletal muscle L-carnitine levels were assessed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, western blotting was used to assess the expression levels of PPARα, CPT1b, pHSL/HSL, and UCP1. HFD treatment increased body/adipose tissue weight, serum FFA levels, circulation L-carnitines and decreased skeletal muscle L-carnitine levels, while HBO treatment alleviated such changes. Moreover, HFD treatment increased fatty acid deposition in adipose tissues and decreased the expression of HSL, while HBO treatment alleviated such changes. Additionally, HFD treatment decreased the expression levels of PPARα and increased those of CPT1b in skeletal muscle, while HBO treatment effectively reverted such changes as well. In brown adipose tissues, HFD increased the expression of UCP1 and the phosphorylation of HSL, which was abolished by HBO treatment as well. In summary, HBO treatment may alleviate HFD-induced fatty acid metabolism dysfunction in C57/B6 mice, which seems to be associated with circulation and skeletal muscle L-carnitine levels and PPARα expression.

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Interactions between the consumption of a high-fat diet and fasting in the regulation of fatty acid oxidation enzyme gene expression: an evaluation of potential mechanisms

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00367.2010 ◽

2011 ◽

Vol 300 (2) ◽

pp. R212-R221 ◽

Cited By ~ 29

Author(s):

Bruce C. Frier ◽

René L. Jacobs ◽

David C. Wright

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Mrna Expression ◽

Protein Content ◽

Fatty Acid Oxidation ◽

P38 Mapk ◽

Acid Oxidation ◽

Plasma Fatty Acid ◽

High Fat ◽

Fed State

The consumption of high-fat diets (HFDs) and fasting are known to increase the expression of enzymes involved in fatty acid oxidation (FAO). However, it has been reported that the ability of physiological stressors to induce enzymes of FAO in skeletal muscle is blunted with obesity. In this regard, we sought to explore the effects and potential mechanisms of an HFD on the expression of FAO enzymes in the fed and fasted state. The consumption of an HFD increased the mRNA expression or protein content of medium-chain acyl-CoA dehydrogenase (MCAD), uncoupling protein-3 (UCP3), and pyruvate dehydrogenase kinase 4 (PDK4) in the fed state. Fasting increased the mRNA expression of PDK4, MCAD, and UCP-3, and the protein content of UCP-3 in chow but not HFD rats. HFDs did not increase carnitine palmitoyl transfer-1 (CPT-1) mRNA levels in the fed state and the effects of fasting were markedly reduced compared with chow-fed rats. The expression of peroxisome-proliferator-activated receptor-γ coactivator-1β (PGC-1β) was increased in muscle from HFD rats in the fed state, while PGC-1-related coactivator (PRC) was increased with fasting in chow-fed but not HFD rats. Plasma fatty acid levels were elevated in the fed state from HFD rats but not increased further with fasting, whereas fasting increased plasma fatty acids in chow-fed animals. Fasting-mediated increases in plasma epinephrine, and the activation of PKA and AMPK in skeletal muscle were similar between chow and HFD rats. p38 MAPK phosphorylation was increased with fasting in chow-fed but not HFD rats. Our findings suggest that a blunted effect of fasting on the induction of PDK4, MCAD, and UCP3 in skeletal muscle from HFD rats is likely a result of already elevated levels of these enzymes, the induction of which is associated with increases in plasma fatty acid and PGC-1β. On the other hand, a blunted induction of PRC and CPT-1 mRNA may be explained by decreases in p38 MAPK signaling.

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Muscle protein synthesis and gene expression during recovery from aerobic exercise in the fasted and fed states

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00348.2010 ◽

2010 ◽

Vol 299 (5) ◽

pp. R1254-R1262 ◽

Cited By ~ 66

Author(s):

Matthew P. Harber ◽

Adam R. Konopka ◽

Bozena Jemiolo ◽

Scott W. Trappe ◽

Todd A. Trappe ◽

...

Keyword(s):

Skeletal Muscle ◽

Aerobic Exercise ◽

Mrna Expression ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Synthesis Rate ◽

Myogenic Regulatory Factor ◽

Expression Of Genes ◽

Dependent Protein ◽

Muscle Protein Metabolism

The purpose of this investigation was to assess mixed-muscle fractional synthesis rate (FSR) and the expression of genes involved in skeletal muscle remodeling after aerobic exercise in the fasted and fed states. Eight recreationally active males (25 ± 1 yr; V̇o2 max: 52 ± 2 ml·kg−1·min−1) performed 60-min of cycle ergometry at 72 ± 1% V̇o2 max on two occasions in a counter-balanced design. Subjects ingested a noncaloric placebo (EX-FAST) or a beverage containing (per kg body wt): 5 kcal, 0.83 g carbohydrate, 0.37 g protein, and 0.03 g fat (EX-FED) immediately and 1 h after exercise. FSR was assessed at rest and following exercise with the use of a l-[ring 2H5]-phenylalanine infusion combined with muscle biopsies at 2 and 6 h postexercise. mRNA expression was assessed at 2 and 6 h postexercise via real-time RT-PCR. FSR was higher ( P < 0.05) after exercise in both EX-FAST (0.112 ± 0.010%·h−1) and EX-FED (0.129 ± 0.014%·h−1) compared with rest (0.071 ± 0.005%·h−1). Feeding attenuated the mRNA expression ( P < 0.05) of proteolytic factors MuRF-1 (6 h) and calpain-2 (2 and 6 h) postexercise but did not alter FOXO3A, calpain-1, caspase3, or myostatin mRNA expression compared with EX-FAST. Myogenic regulatory factor (MRF4) mRNA was also attenuated ( P < 0.05) at 2 and 6 h postexercise in EX-FED compared with EX-FAST. These data demonstrate that a nonexhaustive bout of aerobic exercise stimulates skeletal muscle FSR in the fasted state and that feeding does not measurably enhance FSR between 2 and 6 h after aerobic exercise. Additionally, postexercise nutrient intake attenuates the expression of factors involved in the ubiquitin-proteosome and Ca2+-dependent protein degradation pathways. These data provide insight into the role of feeding on muscle protein metabolism during recovery from aerobic exercise.

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Skeletal Muscle-Specific Keap1 Disruption Modulates Fatty Acid Utilization and Enhances Exercise Capacity in Female Mice

Redox Biology ◽

10.1016/j.redox.2021.101966 ◽

2021 ◽

pp. 101966

Author(s):

Takahiro Onoki ◽

Yoshihiro Izumi ◽

Masatomo Takahashi ◽

Shohei Murakami ◽

Daisuke Matsumaru ◽

...

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Exercise Capacity ◽

Fatty Acid Utilization ◽

Female Mice

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The protein-sparing effect of α-lipoic acid in juvenile grass carp, Ctenopharyngodon idellus: effects on lipolysis, fatty acid β-oxidation and protein synthesis

British Journal Of Nutrition ◽

10.1017/s000711451800226x ◽

2018 ◽

Vol 120 (9) ◽

pp. 977-987 ◽

Cited By ~ 10

Author(s):

Xiao-chen Shi ◽

Ai Jin ◽

Jian Sun ◽

Jing-jing Tian ◽

Hong Ji ◽

...

Keyword(s):

Protein Synthesis ◽

Fatty Acid ◽

Mrna Expression ◽

Lipoic Acid ◽

Grass Carp ◽

Protein Deposition ◽

Experimental Fish ◽

Expression Of Genes ◽

Sparing Effect

AbstractTo investigate the protein-sparing effect of α-lipoic acid (LA), experimental fish (initial body weight: 18·99 (sd 1·82) g) were fed on a 0, 600 or 1200 mg/kg α-LA diet for 56 d, and hepatocytes were treated with 20 μm compound C, the inhibitor of AMP kinase α (AMPKα), treated for 30 min before α-LA treatment for 24 h. LA significantly decreased lipid content of the whole body and other tissues (P<0·05), and it also promoted protein deposition in vivo (P<0·05). Further, dietary LA significantly decreased the TAG content of serum and increased the NEFA content of serum (P<0·05); however, there were no significant differences among all groups in the hepatopancreas and muscle (P>0·05). Consistent with results from the experiment in vitro, LA activated phosphorylation of AMPKα and notably increased the protein content of adipose TAG lipase in intraperitoneal fat, hepatopancreas and muscle in vivo (P<0·05). Meanwhile, LA significantly up-regulated the mRNA expression of genes involved in fatty acid β-oxidation in the same three areas, and LA also obviously down-regulated the mRNA expression of genes involved in amino acid catabolism in muscle (P<0·05). Besides, it was observed that LA significantly activated the mammalian target of rapamycin (mTOR) pathway in muscle of experimental fish (P<0·05). LA could promote lipolysis and fatty acid β-oxidation via increasing energy supply from lipid catabolism, and then, it could economise on the protein from energy production to increase protein deposition in grass carp. Besides, LA might directly promote protein synthesis through activating the mTOR pathway.

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