Research Article Details
Article ID: | A05064 |
PMID: | 33390398 |
Source: | J Nutr Sci Vitaminol (Tokyo) |
Title: | Gene Expression and Histochemical Analyses in the Fatty Livers of Rats Fed a Histidine-Excess Diet. |
Abstract: | Triglyceride (TG) and cholesterol accumulation are known to occur in the liver of rats fed a histidine-excess (5%) diet, but there are few studies reporting histochemical and molecular biological analyses of the rat liver. The aim of this study was to elucidate the molecular basis of this lipid-accumulation mechanism. Lipid accumulations, tissue section images, and gene expression levels were compared in the livers of rats fed a control or histidine-excess diet for 5 wk (n=8/group). Serum levels of TGs, free fatty acids, total cholesterol, high-density lipoprotein cholesterol, glucose, albumin, and the enzyme activities of aspartate aminotransferase and alanine aminotransferase were also analyzed. In the livers of rats fed a histidine-excess diet, histochemical analyses showed what appeared to be a preliminary stage of nonalcoholic fatty liver, characterized by lipid accumulation around the central vein area and minor fibrosis. However, there were no changes in serum TG or free fatty acid levels. Quantitative PCR analyses showed the up-regulation of FAT/CD36, which is related to the uptake of fatty acids into cells, and the downregulation of two apolipoprotein genes, ApoC3 and ApoE. The mRNA levels of PPARγ, LXRα, and AMPKα in the liver were also reduced by excess histidine intake. The results of this study suggest that steatosis caused by excess histidine intake may be the result of an imbalance between lipid transport from the liver and the uptake of free fatty acids into hepatocytes. |
DOI: | 10.3177/jnsv.66.561 |

Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
---|---|---|---|---|---|
S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
Diseases ID | DO ID | Disease Name | Definition | Class | |
---|---|---|---|---|---|
I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
---|---|---|---|---|---|---|---|
D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |