Fatty Liver

Publication Title: 
Scientific Reports

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.

Villano, Gianmarco
Ruvoletto, Mariagrazia
Ceolotto, Giulio
Quarta, Santina
Calabrese, Fiorella
Turato, Cristian
Tono, Natascia
Biasiolo, Alessandra
Cattelan, Arianna
Merkel, Carlo
Avogaro, Angelo
Gatta, Angelo
Pontisso, Patrizia
Publication Title: 
The Journal of Clinical Investigation

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.

Escande, Carlos
Chini, Claudia C. S.
Nin, Veronica
Dykhouse, Katherine Minter
Novak, Colleen M.
Levine, James
Van Deursen, Jan
Gores, Gregory J.
Chen, Junjie
Lou, Zhenkun
Chini, Eduardo Nunes
Publication Title: 
Toxicology and Applied Pharmacology

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.

Huang, Tom Hsun-Wei
Peng, Gang
Li, George Qian
Yamahara, Johji
Roufogalis, Basil D.
Li, Yuhao
Publication Title: 
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.

Rong, Xianglu
Kim, Moon Sun
Su, Ning
Wen, Suping
Matsuo, Yukimi
Yamahara, Johji
Murray, Michael
Li, Yuhao
Publication Title: 
Journal of Acupuncture and Meridian Studies

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.

Suriyavathana Vedanarayanan, M.
Krishnan, Nandhini
Publication Title: 
Journal of Biochemical and Molecular Toxicology

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.

Oz, Helieh S.
Im, Hee-Jeong
Chen, Theresa S.
de Villiers, Willem J. S.
McClain, Craig J.
Publication Title: 
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).

Prudova, Anna
Bauman, Zachary
Braun, Aaron
Vitvitsky, Victor
Lu, Shelly C.
Banerjee, Ruma
Publication Title: 
Digestive Diseases and Sciences

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).

Oz, Helieh S.
Chen, Theresa S.
Neuman, Manuela
Publication Title: 
The Journal of Nutrition

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.

Bruno, Richard S.
Dugan, Christine E.
Smyth, Joan A.
DiNatale, Dana A.
Koo, Sung I.
Publication Title: 
Hepatology (Baltimore, Md.)

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.

Martínez-Chantar, M. Luz
Vázquez-Chantada, Mercedes
Ariz, Usue
Martínez, Núria
Varela, Marta
Luka, Zigmund
Capdevila, Antonieta
Rodríguez, Juan
Aransay, Ana M.
Matthiesen, Rune
Yang, Heping
Calvisi, Diego F.
Esteller, Manel
Fraga, Mario
Lu, Shelly C.
Wagner, Conrad
Mato, José M.


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