The physiological roles of the protease inhibitor SERPINB3 (SB3) are still largely unknown. The study was addressed to assess the biological effects of this serpin in vivo using a SB3 transgenic mouse model. Two colonies of mice (123 transgenic for SB3 and 148 C57BL/6J controls) have been studied. Transgenic (TG) mice showed longer survival than controls and the difference was more remarkable in males than in females (18.5% vs 12.7% life span increase). In TG mice decreased IL-6 in serum and lower p66shc in the liver were observed.
The enzyme sirtuin 1 (SIRT1) is a critical regulator of many cellular functions, including energy metabolism. However, the precise mechanisms that modulate SIRT1 activity remain unknown. As SIRT1 activity in vitro was recently found to be negatively regulated by interaction with the deleted in breast cancer-1 (DBC1) protein, we set out to investigate whether DBC1 regulates SIRT1 activity in vivo. We found that DBC1 and SIRT1 colocalized and interacted, and that DBC1 modulated SIRT1 activity, in multiple cell lines and tissues.
Salacia oblonga (SO) root is an Ayurvedic medicine with anti-diabetic and anti-obese properties. Peroxisome proliferator-activated receptor (PPAR)-alpha, a nuclear receptor, plays an important role in maintaining the homeostasis of lipid metabolism.
Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association
Activation of peroxisome proliferator-activated receptor (PPAR)-alpha by natural and synthetic chemicals induces hepatic hypertrophy. An aqueous extract of Salacia oblonga root (SOW) is an Ayurvedic medicine with anti-diabetic and anti-obesity properties. In the present study, it was found that SOW (100, 300 and 900mg/kg, once daily by oral gavage over a 28 day period) elicited dose-related increases in liver weight (LW) by 1.6%, 13.4% and 42.5%, respectively, and in the ratio of LW to body weight by 8.8%, 16.7% and 40.2%, respectively, in male rats.
Nonalcoholic fatty liver disease (NAFLD) has emerged as a serious obesity-related disorder, and it will continue to be a major liver health issue worldwide in the coming decades. We aimed to determine the effect of Liv-Pro-08 (Nigella sativa, Entada pursaetha, and Ficus glomerata) an oral ayurvedic formulation on rats fed with high-fat diet. Rats were given a high-fat diet for a period of 7 days. After this period, Liv-Pro-08 (250, 500, and 750 mg/kg.body weight was given orally for 7 days.
Nonalcoholic fatty liver (NAFL) and steatohepatitis (NASH) may accompany obesity, diabetes, parenteral nutrition, jejeuno-ileal bypass, and chronic inflammatory bowel disease. Currently there is no FDA approved and effective therapy available. We investigated the potential efficacy of those agents that stimulate glutathione (GSH) biosynthesis on the development of experimental steatohepatitis.
Proceedings of the National Academy of Sciences of the United States of America
The transsulfuration pathway converts homocysteine to cysteine and represents the metabolic link between antioxidant and methylation metabolism. The first and committing step in this pathway is catalyzed by cystathionine beta-synthase (CBS), which is subject to complex regulation, including allosteric activation by the methyl donor, S-adenosylmethionine (AdoMet).
Methionine (Meth) is an essential amino acid involved in DNA methylation and glutathione biosynthesis. We examined the effect of Meth on the development of steatohepatitis. Rats were fed (five weeks) amino acid-based Meth-choline-sufficient (A-MCS) or total deficient (MCD) diets and gavaged daily (two weeks) with vehicle (B-vehicle/MCD), or Meth replacement (C-Meth/MCD). To assess the effect of short-term deficiency, after three weeks one MCS group was fed a deficient diet (D-MCS/MCD).
The incidence of nonalcoholic fatty liver disease (NAFLD) has risen along with the ongoing obesity epidemic. Green tea extract (GTE) inhibits intestinal lipid absorption and may regulate hepatic lipid accumulation. The objective of this study was to determine whether GTE protects against hepatic lipid accumulation during the development of NAFLD in an obese mouse model. Five-wk-old ob/ob (obese) mice and their lean littermates (8 mice x genotype(-1) x dietary treatment(-1)) were fed GTE at 0, 1, or 2% (wt:wt) for 6 wk.
Glycine N-methyltransferase (GNMT) is the main enzyme responsible for catabolism of excess hepatic S-adenosylmethionine (SAMe). GNMT is absent in hepatocellular carcinoma (HCC), messenger RNA (mRNA) levels are significantly lower in livers of patients at risk of developing HCC, and GNMT has been proposed to be a tumor-susceptibility gene for liver cancer. The identification of several children with liver disease as having mutations of the GNMT gene further suggests that this enzyme plays an important role in liver function.