scholarly journals High-fructose feeding does not induce steatosis or non-alcoholic fatty liver disease in pigs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nikolaj H. Schmidt ◽  
Pia Svendsen ◽  
Julián Albarrán-Juárez ◽  
Søren K. Moestrup ◽  
Jacob Fog Bentzon

AbstractNon-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition that has been linked to high-fructose corn syrup consumption with induction of hepatic de novo lipogenesis (DNL) as the suggested central mechanism. Feeding diets very high in fructose (> 60%) rapidly induce several features of NAFLD in rodents, but similar diets have not yet been applied in larger animals, such as pigs. With the aim to develop a large animal NAFLD model, we analysed the effects of feeding a high-fructose (HF, 60% w/w) diet for four weeks to castrated male Danish Landrace-York-Duroc pigs. HF feeding upregulated expression of hepatic DNL proteins, but levels were low compared with adipose tissue. No steatosis or hepatocellular ballooning was seen on histopathological examination, and plasma levels of transaminases were similar between groups. Inflammatory infiltrates and the amount of connective tissue was slightly elevated in liver sections from fructose-fed pigs, which was corroborated by up-regulation of macrophage marker expression in liver homogenates. Supported by RNA-profiling, quantitative protein analysis, histopathological examination, and biochemistry, our data suggest that pigs, contrary to rodents and humans, are protected against fructose-induced steatosis by relying on adipose tissue rather than liver for DNL.

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1822
Author(s):  
Christian von Loeffelholz ◽  
Sina M. Coldewey ◽  
Andreas L. Birkenfeld

5′AMP-activated protein kinase (AMPK) is known as metabolic sensor in mammalian cells that becomes activated by an increasing adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio. The heterotrimeric AMPK protein comprises three subunits, each of which has multiple phosphorylation sites, playing an important role in the regulation of essential molecular pathways. By phosphorylation of downstream proteins and modulation of gene transcription AMPK functions as a master switch of energy homeostasis in tissues with high metabolic turnover, such as the liver, skeletal muscle, and adipose tissue. Regulation of AMPK under conditions of chronic caloric oversupply emerged as substantial research target to get deeper insight into the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Evidence supporting the role of AMPK in NAFLD is mainly derived from preclinical cell culture and animal studies. Dysbalanced de novo lipogenesis has been identified as one of the key processes in NAFLD pathogenesis. Thus, the scope of this review is to provide an integrative overview of evidence, in particular from clinical studies and human samples, on the role of AMPK in the regulation of primarily de novo lipogenesis in human NAFLD.


2021 ◽  
Vol 65 ◽  
pp. 12-20
Author(s):  
Nilay D. Solanki ◽  
Kirti Vadi ◽  
Sandip Patel

Objectives: Non-alcoholic fatty liver disease (NAFLD) is one of the chronic liver diseases. Ficus racemosa has been used for many years in the Ayurvedic medicine system and is closely related with the management of metabolic conditions. The study investigated alleviating effects of methanolic extract of F. racemosa (FRM) bark on high-fat-high-fructose (HFHF) diet -induced NAFLD. Materials and Methods: HFHF-based model was developed for a period of 10 weeks. In treatment groups, FRM (100 mg/kg, 200 mg/kg, and 400 mg/kg) and atorvastatin (20 mg/kg) were administered for 6 weeks after initiating HFHF diet and continued for another 4 weeks. Liver functions test, lipid profile, serum leptin, and antioxidant parameters and histopathology were evaluated. Results: Elevated liver enzymes, lipid markers, and leptin were observed, with significant reduction in antioxidants in disease control rats. FRM treatment significantly improved serum aminotransferase activities, lipid profile, and oxidative changes and brought back to normal. Liver histopathology showed the fatty modifications induced by the HFHF diet, and reduction in fatty changes was observed due to FRM. Significant decline in serum leptin was observed with high-dose FRM. Conclusion: FRM showed positive effects in the reversal of NAFLD and different polyphenolic compounds in the plant were responsible for the proven action.


2006 ◽  
Vol 44 ◽  
pp. S263-S264
Author(s):  
G. Soardol ◽  
C. Pagano ◽  
D. Donnini ◽  
C. Pilone ◽  
L. Domenis ◽  
...  

2020 ◽  
Vol 21 (1) ◽  
pp. 360 ◽  
Author(s):  
Charng-Cherng Chyau ◽  
Hsueh-Fang Wang ◽  
Wen-Juan Zhang ◽  
Chin-Chu Chen ◽  
Shiau-Huei Huang ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified β-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.


2020 ◽  
Vol 11 ◽  
Author(s):  
Silvana Y. Romero-Zerbo ◽  
María García-Fernández ◽  
Vanesa Espinosa-Jiménez ◽  
Macarena Pozo-Morales ◽  
Alejandro Escamilla-Sánchez ◽  
...  

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