scholarly journals Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression

2016 ◽  
Vol 310 (2) ◽  
pp. G103-G116 ◽  
Author(s):  
Simon Musyoka Mwangi ◽  
Sophia Peng ◽  
Behtash Ghazi Nezami ◽  
Natalie Thorn ◽  
Alton B. Farris ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepatic Steatosis ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
High Fat Diet ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
High Fat ◽  
Protein Levels ◽  
Ppar Γ

Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease.

scholarly journals Glial Cell Line Derived Neurotrophic Factor Prevents High Fat Diet Induced Obesity

2011 ◽  
Vol 140 (5) ◽  
pp. S-44
Author(s):  
Simon M. Mwangi ◽  
Smitha Marri ◽  
Behtash G. Nezami ◽  
Ping P. Fu ◽  
Javelin C. Cheng ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity

Su1492 - Glial Cell Line Derived Neurotrophic Factor Prevents High Fat Diet-Induced Hepatic Fibrosis

2018 ◽  
Vol 154 (6) ◽  
pp. S-1157
Author(s):  
Simon M. Mwangi ◽  
Ali Ahmad ◽  
Ge Li ◽  
Shanthi Srinivasan
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Hepatic Fibrosis ◽  
Neurotrophic Factor ◽  
High Fat Diet ◽  
High Fat

Patchouli Oil Attenuates High Fat Diet-induced Non-alcoholic Hepatic Steatosis

Planta Medica ◽  
2020 ◽  
Vol 86 (04) ◽  
pp. 255-266 ◽  
Author(s):  
Nan Xu ◽  
Xue Wu ◽  
Hui-Juan Luo ◽  
Fang-Fang Xu ◽  
Qiong-Hui Huang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
De Novo ◽  
Regulatory Element ◽  
Chinese Herb ◽  
De Novo Lipogenesis ◽  
High Fat ◽  
Very Low Density Lipoproteins ◽  
Alcoholic Fatty Liver

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Nevertheless, no first-line therapy exists. Hepatic steatosis is the earliest stage of NAFLD, which is characterized by an accumulation of hepatic lipids. Patchouli oil (PO), which is isolated from the well-known Chinese herb named Pogostemon cablin (Blanco) Benth. (Lamiaceae), inhibits hepatic lipid accumulation effectively. However, its potential ability for the treatment of NAFLD had not been reported before. Thus, the objective of this study was to investigate the effectiveness of PO against hepatic steatosis and its underlying mechanisms. We used a high fat diet (HFD)-induced hepatic steatosis model of rats to estimate the effect of PO against NAFLD. Hematoxylin-eosin and oil red O staining were used to analyze the hepatic histopathological changes. ELISA, RT-qPCR, and Western blotting analysis were applied to evaluate the parameters for hepatic steatosis. Our results showed that PO significantly attenuated the lipid profiles and the serum enzymes, evidenced by quantitative and histopathological analyses. It also markedly down-regulated the expression of sterol regulatory element-binding protein 1 (SREPB-1c) with its downstream factors in de novo lipogenesis. And, likewise, in lipid export by very low-density lipoproteins (VLDL), related molecules were dramatically improved. Furthermore, PO observably normalized the aberrant peroxisome proliferator-activated receptor α (PPAR-α) signal in fatty acids oxidation. In conclusion, PO exerted a preventing effect against HFD-induced steatosis and might be due to decrease de novo lipogenesis, promote export of lipids, as well as owing to improve fatty acids oxidation.

scholarly journals Glial cell line-derived neurotrophic factor protects against high-fat diet-induced obesity

2014 ◽  
Vol 306 (6) ◽  
pp. G515-G525 ◽  
Author(s):  
Simon Musyoka Mwangi ◽  
Behtash Ghazi Nezami ◽  
Blessing Obukwelu ◽  
Mallappa Anitha ◽  
Smitha Marri ◽  
...  
Keyword(s):  
Weight Gain ◽  
Energy Expenditure ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
High Fat Diet ◽  
High Fat ◽  
Brown Adipocytes ◽  
Diet Induced Obesity

Obesity is a growing epidemic with limited effective treatments. The neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) was recently shown to enhance β-cell mass and improve glucose control in rodents. Its role in obesity is, however, not well characterized. In this study, we investigated the ability of GDNF to protect against high-fat diet (HFD)-induced obesity. GDNF transgenic (Tg) mice that overexpress GDNF under the control of the glial fibrillary acidic protein promoter and wild-type (WT) littermates were maintained on a HFD or regular rodent diet for 11 wk, and weight gain, energy expenditure, and insulin sensitivity were monitored. Differentiated mouse brown adipocytes and 3T3-L1 white adipocytes were used to study the effects of GDNF in vitro. Tg mice resisted the HFD-induced weight gain, insulin resistance, dyslipidemia, hyperleptinemia, and hepatic steatosis seen in WT mice despite similar food intake and activity levels. They exhibited significantly ( P < 0.001) higher energy expenditure than WT mice and increased expression in skeletal muscle and brown adipose tissue of peroxisome proliferator activated receptor-α and β1- and β3-adrenergic receptor genes, which are associated with increased lipolysis and enhanced lipid β-oxidation. In vitro, GDNF enhanced β-adrenergic-mediated cAMP release in brown adipocytes and suppressed lipid accumulation in differentiated 3T3L-1 cells through a p38MAPK signaling pathway. Our studies demonstrate a novel role for GDNF in the regulation of high-fat diet-induced obesity through increased energy expenditure. They show that GDNF and its receptor agonists may be potential targets for the treatment or prevention of obesity.

Loss of regulation of lipogenesis in the Zucker diabetic (ZDF) rat

2000 ◽  
Vol 279 (2) ◽  
pp. E425-E432 ◽  
Author(s):  
W.-N. Paul Lee ◽  
Sara Bassilian ◽  
Shu Lim ◽  
Laszlo G. Boros
Keyword(s):  
High Fat Diet ◽  
Leptin Receptor ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Chain Elongation ◽  
Deuterated Water ◽  
High Fat ◽  
Macronutrient Composition ◽  
Zdf Rat

We present here a study on the role of leptin in the regulation of lipogenesis by examining the effect of dietary macronutrient composition on lipogenesis in the leptin receptor-defective Zucker diabetic fatty rat (ZDF) and its lean litter mate (ZL). Animals were pair fed two isocaloric diets differing in their fat-to-carbohydrate ratio providing 10 and 30% energy as fat. Lipogenesis was measured in the rats using deuterated water and isotopomer analysis. From the deuterium incorporation into plasma palmitate, stearate, and oleate, we determined de novo synthesis of palmitate and synthesis of stearate by chain elongation and of oleate by desaturation. Because the macronutrient composition and the caloric density were controlled, changes in de novo lipogenesis under these dietary conditions represent adaptation to changes in the fat-to-carbohydrate ratio of the diet. De novo lipogenesis was normally suppressed in response to the high-fat diet in the ZL rat to maintain a relatively constant amount of lipids transported. The ZDF rat had a higher rate of lipogenesis, which was not suppressed by the high-fat diet. The results suggest an important hormonal role of leptin in the feedback regulation of lipogenesis.

scholarly journals A high-fat diet suppresses de novo lipogenesis and desaturation but not elongation and triglyceride synthesis in mice

2014 ◽  
Vol 55 (12) ◽  
pp. 2541-2553 ◽  
Author(s):  
Joao A. G. Duarte ◽  
Filipa Carvalho ◽  
Mackenzie Pearson ◽  
Jay D. Horton ◽  
Jeffrey D. Browning ◽  
...  
Keyword(s):  
High Fat Diet ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
High Fat ◽  
Triglyceride Synthesis

scholarly journals Polyunsaturated Fatty Acids Stimulate De novo Lipogenesis and Improve Glucose Homeostasis during Refeeding with High Fat Diet

2017 ◽  
Vol 8 ◽  
Author(s):  
Raffaella Crescenzo ◽  
Arianna Mazzoli ◽  
Rosa Cancelliere ◽  
Francesca Bianco ◽  
Antonia Giacco ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
High Fat
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