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/+ mice were used as the control group. Betaine supplementation significantly alleviated hyperin-sulinemia 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 palmitoyl-transferase 1a mRNA levels, and reduced acetyl-CoA carboxylase activity. Mice fed a betaine-supple-mented 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-ter-minal kinase activity and tau hyperphosphorylation levels were lower in db/db mice fed a betaine-supple-mented 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.
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Abbreviations
- ACC:
-
Acetyl-CoA carboxylase
- AD:
-
Alzheimer’s disease
- BiP:
-
Immunoglobin heavy chain-binding protein
- CPT1a:
-
Carnitine palmitoyltransferase 1a
- eIF2gα:
-
Eukaryotic translation initiation factor 2 alpha
- ER:
-
Endoplasmic reticulum
- GSH:
-
Glu-tathione
- HO-1:
-
Heme oxygenase 1
- HOMA-IR:
-
Homeostatic model assessment of insulin resistance
- JNK:
-
C-Jun N-terminal kinase
- PGC-1gα:
-
Peroxisome proliferator-activated receptor gamma coacti-vator-1 alpha
- PPARgα:
-
Peroxisome proliferator-activated receptor alpha
- RPL19:
-
Ribosomal protein L19
- SCD1:
-
Stearyl-CoA desatu-rase
- TBARS:
-
Thiobarbituric acid reactive substance
- VLDL:
-
very-low-density lipoprotein
- XBP-1:
-
X-box binding protein 1
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Jung, Gy., Won, SB., Kim, J. et al. Betaine Alleviates Hypertriglycemia and Tau Hyperphosphorylation in db/db Mice. Toxicol Res. 29, 7–14 (2013). https://doi.org/10.5487/TR.2013.29.1.007
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DOI: https://doi.org/10.5487/TR.2013.29.1.007