title: Betaine Alleviates Hypertriglycemia and Tau Hyperphosphorylation in db/db Mice.
abstract: Betaine supplementation has been shown to alleviate altered glucose and lipid metabolism in mice fed a high-fat diet or a high-sucrose diet. We investigated the beneficial effects of betaine in diabetic db/db mice. Alleviation of endoplasmic reticulum (ER) and oxidative stress was also examined in the livers and brains of db/db mice fed a betaine-supplemented diet. Male C57BL/KsJ-db/db mice were fed with or without 1% betaine for 5 wk (referred to as the db/db-betaine group and the db/db group, respectively). Lean non-diabetic db/db+ mice were used as the control group. Betaine supplementation significantly alleviated hyperinsulinemia in db/db mice. Betaine reduced hepatic expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha, a major transcription factor involved in gluconeogenesis. Lower serum triglyceride concentrations were also observed in the db/db-betaine group compared to the db/db group. Betaine supplementation induced hepatic peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase 1a mRNA levels, and reduced acetyl-CoA carboxylase activity. Mice fed a betaine-supplemented diet had increased total glutathione concentrations and catalase activity, and reduced lipid peroxidation levels in the liver. Furthermore, betaine also reduced ER stress in liver and brain. c-Jun N-terminal kinase activity and tau hyperphosphorylation levels were lower in db/db mice fed a betaine-supplemented diet, compared to db/db mice. Our findings suggest that betaine improves hyperlipidemia and tau hyperphosphorylation in db/db mice with insulin resistance by alleviating ER and oxidative stress.
authors.affiliation: Department of Food and Nutrition, Seoul National University, Seoul, Korea.
authors.forename: Ga-Young
authors.initials: GY
authors.lastname: Jung
authors.forename: Sae-Bom
authors.initials: SB
authors.lastname: Won
authors.forename: Juhae
authors.initials: J
authors.lastname: Kim
authors.forename: Sookyoung
authors.initials: S
authors.lastname: Jeon
authors.forename: Anna
authors.initials: A
authors.lastname: Han
authors.forename: Young Hye
authors.initials: YH
authors.lastname: Kwon
keywords: Betaine; ER stress; Insulin resistance; Oxidative stress; Tau phosphorylation; db/db mice