Fatty acid synthase inhibition ameliorates diabetes induced liver injury in rodent experimental model.

Abstract

The abnormal dietary life style leads to hyperlipidemia and insulin resistance with ectopic lipid accumulation and elevated levels of hepatic glucose development which are the underlying pathological characteristics of fatty liver diseases. The pharmacological inhibition of fatty acid synthase of de novo lipogenesis may regulate the dysfunctional lipid biotransformation and reverse the pathological state of diabetic liver injury. The three pharmacological interventions (PTS; Pterostilbene, ARB; Arbutin, PUR; Purpurin) were administered to manage the condition of diabetic liver injury against the high fat diet (HFD) + Streptozotocin (STZ) 30 mg/kg b.wt. rodent animal model to observe the effect of abnormal fatty acid synthesis. The qRT-PCR was used to evaluate the fatty acid synthase (FASN) expression which is independently allied with diabetes associated fatty liver disorders. To determine the therapeutic potential of three selected drugs, the biochemical parameters and histopathological considerations were utilized. Three subsequent dosage of PTS, ARB and PUR administered (i.e., 30,60 & 120 mg/kg/p.o.) for five weeks significantly alter the serum parameters, oxidative burden in HFD-STZ which, in turn, resulted in diabetic liver injury. It was also revealed that increased mRNA expression of fatty acid synthase (FASN), which is known to promote abnormal fatty acid synthesis through different molecular signaling pathways, was associated with the development of diabetes associated liver injury, this expression was observed to be significantly suppressed by PTS, ARB and PUR treatment. Moreover, the studies of histopathology showed that there was substantial structural improvement after PTS, ARB and PUR treatment. All three selected drugs have been shown to be effective for Diabetic liver injury (DLI) care but PTS shows impressive results compared to other selected drugs.

• Authors: Onkar Bedi, Niharika Srivastava, Davinder Parsad, Pawan Krishan
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 901 Pg. 174078 (Jun 15 2021) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 33839087 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Anthraquinones
• Antioxidants
• Blood Glucose
• Enzyme Inhibitors
• Stilbenes
• pterostilbene
• Arbutin
• FASN protein, rat
• Fatty Acid Synthase, Type I
• purpurin anthraquinone

Topics

• Animals
• Anthraquinones (therapeutic use)
• Antioxidants (metabolism)
• Arbutin (therapeutic use)
• Blood Glucose (metabolism)
• Diabetes Complications (drug therapy)
• Diabetes Mellitus, Experimental (complications, drug therapy)
• Diet, High-Fat
• Enzyme Inhibitors (therapeutic use)
• Fatty Acid Synthase, Type I (antagonists & inhibitors, biosynthesis, genetics)
• Lipid Metabolism (drug effects)
• Lipid Peroxidation (drug effects)
• Liver Diseases (etiology, prevention & control)
• Male
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)
• Stilbenes (therapeutic use)