Dataset Information

Importance of propionate for the repression of hepatic lipogenesis and improvement of insulin sensitivity in high-fat diet-induced obesity.

ABSTRACT:

Scope

The SCFA acetate (Ac) and propionate (Pr) are major fermentation products of dietary fibers and provide additional energy to the host. We investigated short- and long-term effects of dietary Ac and Pr supplementation on diet-induced obesity and hepatic lipid metabolism.

Methods and results

C3H/HeOuJ mice received high-fat (HF) diets supplemented with 5% SCFA in different Ac:Pr ratios, a high acetate (HF-HAc; 2.5:1 Ac:Pr) or high Pr ratio (HF-HPr; 1:2.5 Ac:Pr) for 6 or 22 weeks. Control diets (low-fat (LF), HF) contained no SCFA. SCFA did not affect body composition but reduced hepatic gene and protein expression of lipogenic enzymes leading to a reduced hepatic triglyceride concentration after 22 weeks in HF-HPr mice. Analysis of long-chain fatty acid composition (liver and plasma phospholipids) showed that supplementation of both ratios led to a lower ?6:?3 ratio. Pr directly led to increased odd-chain fatty acid (C15:0, C17:0) formation as confirmed in vitro using HepG2 cells. Remarkably, plasma C15:0 was correlated with the attenuation of HF diet-induced insulin resistance.

Conclusion

Dependent on the Ac:Pr ratio, especially odd-chain fatty acid formation and insulin sensitivity are differentially affected, indicating the importance of Pr.

SUBMITTER: Weitkunat K

PROVIDER: S-EPMC5215627 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Importance of propionate for the repression of hepatic lipogenesis and improvement of insulin sensitivity in high-fat diet-induced obesity.

Weitkunat Karolin K Schumann Sara S Nickel Daniela D Kappo Katharina Antonia KA Petzke Klaus Jürgen KJ Kipp Anna Patricia AP Blaut Michael M Klaus Susanne S

Molecular nutrition & food research 20160830 12

<h4>Scope</h4>The SCFA acetate (Ac) and propionate (Pr) are major fermentation products of dietary fibers and provide additional energy to the host. We investigated short- and long-term effects of dietary Ac and Pr supplementation on diet-induced obesity and hepatic lipid metabolism.<h4>Methods and results</h4>C3H/HeOuJ mice received high-fat (HF) diets supplemented with 5% SCFA in different Ac:Pr ratios, a high acetate (HF-HAc; 2.5:1 Ac:Pr) or high Pr ratio (HF-HPr; 1:2.5 Ac:Pr) for 6 or 22 wee ...[more]

PMID: 27467905

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Project description:Reduced hepatic glycogenesis is one of the most important causes of metabolic abnormalities in non‑alcoholic fatty liver disease. Octreotide, a somatostatin analogue, has been demonstrated to promote weight loss and improve metabolic disorders in mice with high fat diet (HFD)‑induced obesity. However, whether octreotide affects hepatic glycogenesis is unknown. The aim of the present study was to verify the effects of octreotide on hepatic glycogenesis in rats with HFD‑induced obesity. Male Sprague‑Dawley rats were fed a standard diet or a HFD for 24 weeks. Obese rats from the HFD group were further divided into a HFD‑control group and an octreotide‑administered group. Rats in the latter group were injected with octreotide for 8 days. Glucose and insulin tolerance tests were performed, and the area under the curve (AUC) was calculated. Following sacrifice, their body weights and lengths, fasting plasma glucose (FPG), fasting insulin (FINS), serum triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. In addition, Lee's index and the homeostatic model assessment index were calculated. Hepatic TG, FFA levels and glycogen content were first determined. Hepatic steatosis in the obese rats was assessed based on hematoxylin and eosin and Oil Red O staining. Human hepatoblastoma HepG2 cells were divided into a control group, a palmitate (PA)‑treated group and a PA + octreotide‑treated group. Establishment of the in vitro fatty liver model using HepG2 cells was confirmed by Oil Red O staining. The expression of phosphorylated Akt and glycogen synthase kinase 3β (GSK3β) was detected by western blotting, and glycogen synthase (GS) mRNA levels were detected by reverse transcription‑quantitative polymerase chain reaction. Compared with the control group, the body weight, Lee's index, AUC of the intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test, levels of FPG, FINS, TG, TC, FFA, ALT and AST, and HOMA index values were significantly increased in the obese rats. The body weight, levels of FPG and FINS, and the HOMA index were significantly reduced following octreotide treatment, whereas the decrease in Lee's index, the blood levels of ALT, AST, TC, TG and FFA, and the AUC did not reach statistical significance. Hepatic TG and FFA levels were significantly increased and hepatic glycogen content was significantly decreased in rats with HFD‑induced obesity when compared with those in the control group. Octreotide intervention restored these alterations. The expression levels of phosphorylated Akt and GSK3β protein expression, as well as GS mRNA levels in the HFD group were lower when compared with those in the control group, whereas octreotide treatment reversed these reductions. The in vitro experiments demonstrated that the reduced levels of phosphorylated Akt and GSK3β protein, and GS mRNA in the PA‑treated group were significantly reversed by octreotide treatment. In conclusion, the results indicate that octreotide improved hepatic glycogenesis and decreased FPG concentration in rats with HFD‑induced obesity. These mechanisms may be associated with increased GS activity via the promotion of GSK3β phosphorylation. Therefore, octreotide may be regarded as a novel therapeutic strategy for HFD‑induced obesity and obesity‑associated metabolic disorders.

Dataset Information

Importance of propionate for the repression of hepatic lipogenesis and improvement of insulin sensitivity in high-fat diet-induced obesity.

Scope

Methods and results

Conclusion

Publications

Importance of propionate for the repression of hepatic lipogenesis and improvement of insulin sensitivity in high-fat diet-induced obesity.

Similar Datasets

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