n-Butanol Extract of Lotus Seeds Exerts Antiobesity Effects in 3T3-L1 Preadipocytes and High-Fat Diet-Fed Mice via Activating Adenosine Monophosphate-Activated Protein Kinase

Background/Aims: Obesity-associated fatty liver disease affects millions of individuals. This study aimed to evaluate the therapeutic effects of baicalin to treat obesity and fatty liver in high fat diet-induced obese mice, and to study the potential molecular mechanisms. Methods: High fat diet-induced obese animals were treated with different doses of baicalin (100, 200 and 400 mg/kg/d). Whole body, fat pad and liver were weighed. Hyperlipidemia, liver steatosis, liver function, and hepatic Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ) / AMP-activated protein kinase (AMPK) / acetyl-CoA carboxylase (ACC) were further evaluated. Results: Baicalin significantly decreased liver, epididymal fat and body weights in high fat diet-fed mice, which were associated with decreased serum levels of triglycerides, total cholesterol, LDL, alanine transaminase and aspartate transaminase, but increased serum HDL level. Pathological analysis revealed baicalin dose-dependently decreased the degree of hepatic steatosis, with predominantly diminished macrovesicular steatosis at lower dose but both macrovesicular and microvesicular steatoses at higher dose of baicalin. Baicalin dose-dependently inhibited hepatic CaMKKβ/AMPK/ACC pathway. Conclusion: These data suggest that baicalin up to 400 mg/kg/d is safe and able to decrease the degree of obesity and fatty liver diseases. Hepatic CaMKKβ/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.

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Viola mandshurica ethanolic extract prevents high-fat-diet-induced obesity in mice by activating AMP-activated protein kinase

Environmental Toxicology and Pharmacology ◽

10.1016/j.etap.2014.04.028 ◽

2014 ◽

Vol 38 (1) ◽

pp. 41-50 ◽

Cited By ~ 10

Author(s):

Yoon-Young Sung ◽

Dong-Seon Kim ◽

Ho Kyoung Kim

Keyword(s):

Protein Kinase ◽

High Fat Diet ◽

Ethanolic Extract ◽

High Fat ◽

Diet Induced Obesity ◽

Obesity In Mice ◽

Amp Activated Protein Kinase

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S2047 Adiponectin Suppresses Colorectal Carcinogenesis Induced By High-Fat Diet via AMP Protein Kinase

Gastroenterology ◽

10.1016/s0016-5085(08)61417-1 ◽

2008 ◽

Vol 134 (4) ◽

pp. A-304

Author(s):

Nobutaka Fujisawa ◽

Atsushi Nakajima

Keyword(s):

Protein Kinase ◽

High Fat Diet ◽

Colorectal Carcinogenesis ◽

High Fat

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Amyotrophy Induced by a High-Fat Diet Is Closely Related to Inflammation and Protein Degradation Determined by Quantitative Phosphoproteomic Analysis in Skeletal Muscle of C57BL/6 J Mice

Journal of Nutrition ◽

10.1093/jn/nxz236 ◽

2019 ◽

Vol 150 (2) ◽

pp. 294-302

Author(s):

Ya-nan Sun ◽

Jia-qiang Huang ◽

Zhong-zhou Chen ◽

Min Du ◽

Fa-zheng Ren ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Protein Kinase ◽

Glucose Metabolism ◽

Protein Degradation ◽

Muscle Atrophy ◽

High Fat Diet ◽

Molecular Mechanisms ◽

Serum Glucose ◽

High Fat

ABSTRACT Background Ectopic fat accumulation in skeletal muscle results in dysfunction and atrophy, but the underlying molecular mechanisms remain unclear. Objective The aim of this study was to investigate the effects of a high-fat diet (HFD) in modulating the structure and energy metabolism of skeletal muscle and the underlying mechanisms in mice. Methods Four-week-old male C57BL/6 J mice (n = 30) were allowed 1 wk for acclimatization. After 6 mice with low body weight were removed from the study, the remaining 24 mice were fed with a normal-fat diet (NFD; 10% energy from fat, n = 12) or an HFD (60% energy from fat, n = 12) for 24 wk. At the end of the experiment, serum glucose and lipid concentrations were measured, and skeletal muscle was collected for atrophy analysis, inflammation measurements, and phosphoproteomic analysis. Results Compared with the NFD, the HFD increased (P < 0.05) body weight (35.8%), serum glucose (64.5%), and lipid (27.3%) concentrations, along with elevated (P < 0.05) expressions of the atrophy-related proteins muscle ring finger 1 (MURF1; 27.6%) and muscle atrophy F-box (MAFBX; 44.5%) in skeletal muscle. Phosphoproteomic analysis illustrated 64 proteins with differential degrees of phosphorylation between the HFD and NFD groups. These proteins were mainly involved in modulating cytoskeleton [adenylyl cyclase-associated protein 2 (CAP2) and actin-α skeletal muscle (ACTA1)], inflammation [NF-κB-activating protein (NKAP) and serine/threonine-protein kinase RIO3 (RIOK3)], glucose metabolism [Cdc42-interacting protein 4 (TRIP10); protein kinase C, and casein kinase II substrate protein 3 (PACSIN3)], and protein degradation [heat shock protein 90 kDa (HSP90AA1)]. The HFD-induced inhibitions of the insulin signaling pathway and activations of inflammation in skeletal muscle were verified by Western blot analysis. Conclusions Quantitative phosphoproteomic analysis in C57BL/6 J mice fed an NFD or HFD for 24 wk revealed that the phosphorylation of inflammatory proteins and proteins associated with glucose metabolism at specific serine residues may play critical roles in the regulation of skeletal muscle atrophy induced by an HFD. This work provides information regarding underlying molecular mechanisms for inflammation-induced dysfunction and atrophy in skeletal muscle.

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Increased Insulin Sensitivity by High-Altitude Hypoxia in Mice with High-Fat Diet-Induced Obesity Is Associated with Activated AMPK Signaling and Subsequently Enhanced Mitochondrial Biogenesis in Skeletal Muscles

Obesity Facts ◽

10.1159/000508112 ◽

2020 ◽

Vol 13 (5) ◽

pp. 455-472

Author(s):

Kang Song ◽

Yifan Zhang ◽

Qin Ga ◽

Zhenzhong Bai ◽

Ri-Li Ge

Keyword(s):

Fatty Acid ◽

Insulin Sensitivity ◽

Protein Kinase ◽

High Altitude ◽

Mitochondrial Biogenesis ◽

High Fat Diet ◽

Skeletal Muscles ◽

Acid Oxidation ◽

High Fat ◽

Low Altitude

Background: This study aimed to investigate whether and how high altitude-associated ambient hypoxia affects insulin sensitivity in mice fed a high-fat diet (HFD). Methods: Mice were randomly divided into a control group (with normal diet feeding and low-altitude housing), LA/HFD group (with HFD feeding and low-altitude housing), and HA/HFD group (with HFD feeding and high-altitude housing). Results: After 8 weeks, mice in the HA/HFD group showed improved insulin sensitivity-related indices compared with the LA/HFD group. In mice residing in a low-altitude region, HFD significantly impaired mitochondrial respiratory function and mitochondrial DNA content in skeletal muscles, which was partially reversed in mice in the HA/HFD group. In addition, the fatty acid oxidation-related enzyme gene CPT1 (carnitine palmitoyltransferase 1) and genes related to mitochondrial biogenesis such as peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (Tfam) were upregulated in the skeletal muscles of mice housed at high altitude, in comparison to in the LA/HFD group. Furthermore, AMPK (adenosine monophosphate-activated protein kinase) signaling was activated in the skeletal muscles, as evidenced by a higher expression of phosphorylated AMPK (p-AMPK) and protein kinase B (p-AKT) in the HA/HFD group than in the LA/HFD group. Conclusion: Our study suggests that high-altitude hypoxia improves insulin sensitivity in mice fed an HFD, which is associated with AMPK activation in the skeletal muscle and consequently enhanced mitochondrial biogenesis and fatty acid oxidation. This work provides a molecular explanation for why high altitude is associated with a reduced incidence of insulin resistance in the obese population.

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