Dietary eicosapentaenoic acid supplementation accentuates hepatic triglyceride accumulation in mice with impaired fatty acid oxidation capacity

Ovarian hormone deficiency leads to increased body weight, visceral adiposity, fatty liver and disorders associated with menopausal metabolic syndrome. To better understand the underlying mechanisms of these disorders in their early phases of development, we investigated the effect of ovariectomy on lipid and glucose metabolism. Compared to sham-operated controls, ovariectomized Wistar female rats markedly increased whole body and visceral adipose tissue weight (p ˂ 0.05) and exhibited insulin resistance in peripheral tissues. Severe hepatic triglyceride accumulation (p ˂ 0.001) after ovariectomy preceded changes in both serum lipids and glucose intolerance, reflecting alterations in some CYP proteins. Increased CYP2E1 (p ˂ 0.05) and decreased CYP4A (p ˂ 0.001) after ovariectomy reduced fatty acid oxidation and induced hepatic steatosis. Decreased triglyceride metabolism and secretion from the liver contributed to hepatic triglyceride accumulation in response to ovariectomy. In addition, interscapular brown adipose tissue of ovariectomized rats exhibited decreased fatty acid oxidation (p ˂ 0.01), lipogenesis (p ˂ 0.05) and lipolysis (p ˂ 0.05) despite an increase in tissue weight. The results provide evidence that impaired hepatic triglycerides and dysregulation of some CYP450 proteins may have been involved in the development of hepatic steatosis. The low metabolic activity of brown adipose tissue may have contributed to visceral adiposity as well as triglyceride accumulation during the postmenopausal period.

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Liver-specific deletion of IGF2 mRNA binding protein-2/IMP2 reduces hepatic fatty acid oxidation and increases hepatic triglyceride accumulation

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.008778 ◽

2019 ◽

Vol 294 (31) ◽

pp. 11944-11951 ◽

Cited By ~ 6

Author(s):

Laura Regué ◽

Liliana Minichiello ◽

Joseph Avruch ◽

Ning Dai

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Binding Protein ◽

Acid Oxidation ◽

Hepatic Triglyceride ◽

Triglyceride Accumulation ◽

Mrna Binding Protein ◽

Hepatic Fatty Acid Oxidation ◽

Mrna Binding ◽

Specific Deletion

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Farnesol, an isoprenoid, improves metabolic abnormalities in mice via both PPARα-dependent and -independent pathways

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00061.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. E1022-E1032 ◽

Cited By ~ 35

Author(s):

Tsuyoshi Goto ◽

Young-Il Kim ◽

Kozue Funakoshi ◽

Aki Teraminami ◽

Taku Uemura ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Target Genes ◽

Farnesoid X Receptor ◽

Luciferase Assay ◽

Acid Oxidation ◽

Metabolic Abnormalities ◽

Hepatic Triglyceride ◽

Wild Type ◽

Triglyceride Accumulation

Peroxisome proliferator-activated receptors (PPARs) control energy homeostasis. In this study, we showed that farnesol, a naturally occurring ligand of PPARs, could ameliorate metabolic diseases. Obese KK-Ay mice fed a high-fat diet (HFD) containing 0.5% farnesol showed significantly decreased serum glucose level, glucosuria incidence, and hepatic triglyceride contents. Farnesol-containing HFD upregulated the mRNA expressions of PPARα target genes involved in fatty acid oxidation in the liver. On the other hand, farnesol was not effective in upregulating the mRNA expressions of PPARγ target genes in white adipose tissues. Experiments using PPARα-deficient [(−/−)] mice revealed that the upregulation of fatty acid oxidation-related genes required PPARα function, but the suppression of hepatic triglyceride accumulation was partially PPARα-dependent. In hepatocytes isolated from the wild-type and PPARα (−/−) mice, farnesol suppressed triglyceride synthesis. In luciferase assay, farnesol activated both PPARα and the farnesoid X receptor (FXR) at similar concentrations. Moreover, farnesol increased the mRNA expression level of a small heterodimer partner known as one of the FXR target genes and decreased those of sterol regulatory element-binding protein-1c and fatty acid synthase in both the wild-type and PPARα (−/−) hepatocytes. These findings suggest that farnesol could improve metabolic abnormalities in mice via both PPARα-dependent and -independent pathways and that the activation of FXR by farnesol might contribute partially to the PPARα-independent hepatic triglyceride content-lowering effect. To our knowledge, this is the first study on the effect of the dual activators of PPARα and FXR on obesity-induced metabolic disorders.

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A Low-Carbohydrate Ketogenic Diet and Treadmill Training Enhanced Fatty Acid Oxidation Capacity but Did Not Enhance Maximal Exercise Capacity in Mice

Nutrients ◽

10.3390/nu13020611 ◽

2021 ◽

Vol 13 (2) ◽

pp. 611

Author(s):

Sihui Ma ◽

Jiao Yang ◽

Takaki Tominaga ◽

Chunhong Liu ◽

Katsuhiko Suzuki

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Exercise Capacity ◽

Ketogenic Diet ◽

Maximal Exercise ◽

Treadmill Running ◽

Acid Oxidation ◽

Oxidation Capacity ◽

Low Carbohydrate ◽

Maximal Exercise Capacity

The low-carbohydrate ketogenic diet (LCKD) is a dietary approach characterized by the intake of high amounts of fat, a balanced amount of protein, and low carbohydrates, which is insufficient for metabolic demands. Previous studies have shown that an LCKD alone may contribute to fatty acid oxidation capacity, along with endurance. In the present study, we combined a 10-week LCKD with an 8-week forced treadmill running program to determine whether training in conjunction with LCKD enhanced fatty acid oxidation capacity, as well as whether the maximal exercise capacity would be affected by an LCKD or training in a mice model. We found that the lipid pool and fatty acid oxidation capacity were both enhanced following the 10-week LCKD. Further, key fatty acid oxidation related genes were upregulated. In contrast, the 8-week training regimen had no effect on fatty acid and ketone body oxidation. Key genes involved in carbohydrate utilization were downregulated in the LCKD groups. However, the improved fatty acid oxidation capacity did not translate into an enhanced maximal exercise capacity. In summary, while favoring the fatty acid oxidation system, an LCKD, alone or combined with training, had no beneficial effects in our intensive exercise-evaluation model. Therefore, an LCKD may be promising to improve endurance in low- to moderate-intensity exercise, and may not be an optimal choice for those partaking in high-intensity exercise.

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