Beneficial effects of the ketogenic diet on glucose intolerance and hepatic lipid accumulation in obese mice model

Non-alcoholic fatty liver disease is strongly associated with obese and type 2 diabetes. It has been reported that an oxidized cholesterol, 7-ketocholesterol (7KC), might cause inflammatory response in macrophages and plasma 7KC concentration were higher in patients with cardiovascular diseases or diabetes. Therefore, we have decided to test whether small amount of 7KC in diet might induce hepatic steatosis and inflammation in two types of obese models. We found that addition of 0.01% 7KC either in chow diet (CD, regular chow diet with 1% cholesterol) or western type diet (WD, high fat diet with 1% cholesterol) accelerated hepatic neutral lipid accumulation by Oil Red O staining. Importantly, by lipid extraction analysis, it has been recognized that triglyceride rather than cholesterol species was significantly accumulated in CD+7KC compared to CD as well as in WD+7KC compared to WD. Immunostaining revealed that macrophages infiltration was increased in CD+7KC compared to CD, and also in WD+7KC compared to WD. These phenotypes were accompanied by inducing inflammatory response and downregulating fatty acid oxidation. Furthermore, RNA sequence analysis demonstrated that 7KC reduced expression of genes which related to autophagy process. Levels of LC3-II protein were decreased in WD+7KC compared to WD. Similarly, we have confirmed the effect of 7KC on acceleration of steatohepatitis in db/db mice model. Collectively, our study has demonstrated that small amount of dietary 7KC contributed to accelerate hepatic steatosis and inflammation in obese mice models.

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Lemon Balm Extract ALS-L1023 Regulates Obesity and Improves Insulin Sensitivity via Activation of Hepatic PPARα in High-Fat Diet-Fed Obese C57BL/6J Mice

International Journal of Molecular Sciences ◽

10.3390/ijms21124256 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4256

Author(s):

Dongju Lee ◽

Yujin Shin ◽

Jong Seong Roh ◽

Jiwon Ahn ◽

Sunhyo Jeoong ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Insulin Sensitivity ◽

Lipid Accumulation ◽

High Fat Diet ◽

Obese Mice ◽

High Fat ◽

Lemon Balm ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation

Our previous studies demonstrated that peroxisome proliferator-activated receptor α (PPARα) activation reduces weight gain and improves insulin sensitivity in obese mice. Since excess lipid accumulation in non-adipose tissues is suggested to be responsible for the development of insulin resistance, this study was undertaken to examine whether the lemon balm extract ALS-L1023 regulates hepatic lipid accumulation, obesity, and insulin resistance and to determine whether its mechanism of action involves PPARα. Administration of ALS-L1023 to high-fat-diet-induced obese mice caused reductions in body weight gain, visceral fat mass, and visceral adipocyte size without changes of food consumption profiles. ALS-L1023 improved hyperglycemia, hyperinsulinemia, glucose and insulin tolerance, and normalized insulin-positive β-cell area in obese mice. ALS-L1023 decreased hepatic lipid accumulation and concomitantly increased the expression of PPARα target genes responsible for fatty acid β-oxidation in livers. In accordance with the in vivo data, ALS-L1023 reduced lipid accumulation and stimulated PPARα reporter gene expression in HepG2 cells. These effects of ALS-L1023 were comparable to those of the PPARα ligand fenofibrate, while the PPARα antagonist GW6471 inhibited the actions of ALS-L1023 on lipid accumulation and PPARα luciferase activity in HepG2 cells. Higher phosphorylated protein kinase B (pAkt)/Akt ratios and lower expression of gluconeogenesis genes were observed in the livers of ALS-L1023-treated mice. These results indicate that ALS-L1023 may inhibit obesity and improve insulin sensitivity in part through inhibition of hepatic lipid accumulation via hepatic PPARα activation.

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Houttuynia cordata Thunb. Attenuates Hepatic Lipid Accumulation in Diet-Induced Obese Mice

Journal of the Korean Society of Food Science and Nutrition ◽

10.3746/jkfn.2021.50.9.895 ◽

2021 ◽

Vol 50 (9) ◽

pp. 895-903

Author(s):

Su-Jung Cho ◽

O-Jun Kwon

Keyword(s):

Lipid Accumulation ◽

Obese Mice ◽

Houttuynia Cordata ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation ◽

Houttuynia Cordata Thunb

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Sirt1 and Sirt6 Mediate Beneficial Effects of Rosiglitazone on Hepatic Lipid Accumulation

PLoS ONE ◽

10.1371/journal.pone.0105456 ◽

2014 ◽

Vol 9 (8) ◽

pp. e105456 ◽

Cited By ~ 12

Author(s):

Soo Jin Yang ◽

Jung Mook Choi ◽

Eugene Chang ◽

Sung Woo Park ◽

Cheol-Young Park

Keyword(s):

Lipid Accumulation ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation ◽

Beneficial Effects

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ERK-dependent mTOR pathway is involved in berberine-induced autophagy in hepatic steatosis

Journal of Molecular Endocrinology ◽

10.1530/jme-16-0139 ◽

2016 ◽

Vol 57 (4) ◽

pp. 251-260 ◽

Cited By ~ 15

Author(s):

Qin He ◽

Dan Mei ◽

Sha Sha ◽

Shanshan Fan ◽

Lin Wang ◽

...

Keyword(s):

Hepatic Steatosis ◽

Lipid Accumulation ◽

Mtor Pathway ◽

Mice Model ◽

Alcoholic Fatty Liver ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation ◽

Positive Effects

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem and is considered as a hepatic manifestation of metabolic syndrome. Increasing evidence demonstrates that berberine (BBR), a natural plant alkaloid, is beneficial for obesity-associated NAFLD. However, the mechanisms about how BBR improves hepatic steatosis remain uncertain. Recently, some reports revealed that enhanced autophagy could decrease hepatic lipid accumulation. In this study, we first established a high-fed diet (HFD) mice model and oleate–palmitate-induced lipotoxicity hepatocytes to explore the association among BBR, autophagy and hepatic steatosis. Our data demonstrated that BBR had profound effects on improving hepatic lipid accumulation bothin vivoandin vitro, and led to high autophagy flux. The molecular alterations proceeding these changes were characterized by inhibition of the ERK/mTOR pathway. These findings suggest an important mechanism for the positive effects of BBR on hepatic steatosis, and may provide new evidence for the clinical use of BBR in NAFLD.

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