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. 2016 Feb 18;8(2):100.
doi: 10.3390/nu8020100.

Allomyrina Dichotoma Larvae Regulate Food Intake and Body Weight in High Fat Diet-Induced Obese Mice Through mTOR and Mapk Signaling Pathways

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Free PMC article

Allomyrina Dichotoma Larvae Regulate Food Intake and Body Weight in High Fat Diet-Induced Obese Mice Through mTOR and Mapk Signaling Pathways

Jongwan Kim et al. Nutrients. .
Free PMC article

Abstract

Recent evidence has suggested that the Korean horn beetle (Allomyrina dichotoma) has anti-hepatofibrotic, anti-neoplastic, and antibiotic effects and is recognized as a traditional medicine. In our previous works, Allomyrina dichotoma larvae (ADL) inhibited differentiation of adipocytes both in vitro and in vivo. However, the anorexigenic and endoplasmic reticulum(ER) stress-reducing effects of ADL in obesity has not been examined. In this study, we investigated the anorexigenic and ER stress-reducing effects of ADL in the hypothalamus of diet-induced obese (DIO) mice. Intracerebroventricular (ICV) administration of ethanol extract of ADL (ADE) suggested that an antagonizing effect on ghrelin-induced feeding behavior through the mTOR and MAPK signaling pathways. Especially, ADE resulted in strong reduction of ER stress both in vitro and in vivo. These findings strongly suggest that ADE and its constituent bioactive compounds are available and valuable to use for treatment of various diseases driven by prolonged ER stress.

Keywords: Allomyrina dichotoma larvae; ER stress; appetite; diet-induced obesity; hypothalamus.

Figures

Figure 1
Figure 1
Increased hypothalamic ER stress in mice fed a high-fat diet. (A) Experimental timeline of the experimental procedure; (B) Time dependence of body weight in low fat and high-fat-diet-induced mice. At 8 weeks of age, mice fed a high-fat diet showed a 43% increase in body weight compared with those fed a low-fat diet. The results are means ± SDs (n = 10); * p values of < 0.05 indicate significant difference from low-fat diet-induced mice; (C) mRNA expression levels of ER stress responsive markers in low fat and high-fat-diet-induced mice. mRNA expression levels of ER stress responsive markers were dramatically upregulated in high-fat-diet-induced obese mice. The results are means ± SDs (n = 10); * p values of < 0.05 indicate significant difference from low-fat-diet-induced mice. LF, low-fat diet. HF, high-fat diet.
Figure 2
Figure 2
Effects of central administration of ADE on food intake and body weight. The average cumulative food intake (A) and body weight (B) were measured in high-fat-diet-induced mice ICV administration with ADE (1 μL of 10 mg/mL) or DMSO (1 μL of 20% DMSO) during the experimental period. The results are means ± SDs (n = 10 per group); * p values of < 0.05 indicate significant difference from administration with DMSO (1 μL of 20% DMSO). (C) Effects of ICV administration of ADE (1 μL of 10 mg/mL) on hypothalamic mRNA expression levels of neuropeptides. The results are means ± SDs (n = 10 per group); * p values of < 0.05 indicate significant difference from administration with DMSO (1 μL of 20% DMSO). ADE, ethanol extract of Allomyrina dichotoma larvae. HF, high-fat diet with DMSO. HFA, high-fat diet with ADE.
Figure 3
Figure 3
Effects of central administration of ADE on ER stress responsive markers and ER chaperone/foldases expression. (A) Effects of ICV administration of ADE (1 μL of 10 mg/mL) on hypothalamic ER stress responsive markers and ER chaperone/foldases. The results of densitometric analysis (lower) are means ± SDs (n = 10); * p values of < 0.05 indicate significant difference from administration with DMSO (1 μL of 20% DMSO); (B) Effects of ICV administration of ADE (1 μL of 10 mg/mL) on hypothalamic mRNA expression levels of hypothalamic ER stress responsive markers. The results are means ± SDs (n = 10 per group); * p values of < 0.05 indicate significant difference from administration with DMSO (1 μL of 20% DMSO). HF, high-fat diet with DMSO. HFA, high-fat diet with ADE.
Figure 4
Figure 4
Central administration of ADE reduces ghrelin signaling through mTOR and ERK signaling pathways in mice fed a high-fat diet. (A) Effects of ICV administration of ADE (1 μL of 10 mg/mL) on mTOR signaling pathways. The results of densitometric analysis (right) are means ± SDs (n = 10 per group); * p values of < 0.05 indicate significant difference from administration with DMSO (1 μL of 20% DMSO); (B) Effects of ICV administration of ADE (1 μL of 10 mg/mL) on MAPK signaling pathways. The results of densitometric analysis (right) are means ± SDs (n = 10); * p values of < 0.05 indicate significant difference from administration with DMSO (1 μL of 20% DMSO). HF, high-fat diet with DMSO. HFA, high-fat diet with ADE.

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