Betaine Alleviates High-Fat Diet-Induced Disruptionof Hepatic Lipid and Iron Homeostasis in Mice

Abstract

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat deposition in the liver, which is often associated with disrupted iron homeostasis. Betaine has been reported to be hepatoprotective, yet whether and how betaine ameliorates high-fat diet-induced disruption of hepatic lipid and iron homeostasis remains elusive. In this study, mice were fed either standard (CON) or high-fat diet (HFD) for 9 weeks to establish a NAFLD model. Mice raised on HF diet were then assigned randomly to HF and HFB groups, HFB group being supplemented with 1% (w/v) of betaine in the drinking water for 13 weeks. Betaine supplementation significantly alleviated excessive hepatic lipid deposition and restored hepatic iron content. Betaine partly yet significantly reversed HFD-induced dysregulation of lipogenic genes such as PRARγ and CD36, as well as the iron-metabolic genes including FPN and HAMP that encodes hepcidin. Similar mitigation effects of betaine were observed for BMP2 and BMP6, the up-stream regulators of hepcidin expression. Betaine significantly rectified disrupted expression of methyl transfer gene, including BHMT, GNMT and DNMT1. Moreover, HFD-modified CpG methylation on the promoter of PRARγ and HAMP genes was significantly reversed by betaine supplementation. These results indicate that betaine alleviates HFD-induced disruption of hepatic lipid and iron metabolism, which is associated with modification of CpG methylation on promoter of lipogenic and iron-metabolic genes.

Mutation in Smek2 regulating hepatic glucose metabolism causes hypersarcosinemia and hyperhomocysteinemia in rats

“…But, BHMT protein levels were not changed in this study. There is a report that BHMT protein was also proportionally decreased linked to mRNA levels in high-fat-diet fed mouse 37 . As another possibility that BHMT protein levels did not reflect mRNA levels, Smek2 dysfunction may affect BHMT protein regulation in the liver.…”

The Protective Effect of Lycium barbarum Betaine and Effervescent Tablet Against Carbon Tetrachloride-Induced Acute Liver Injury in Rats

“…A recent study showed that betaine reduces the disruption of hepatic lipid and iron homeostasis caused by a high-fat diet in mice. 46 Another study showed that betaine could alleviate liver damage caused by ionizing radiation. 47 As a functional food or pharmaceutical formulation, effervescent tablets can be used as a new formulation for patients who have difficulty swallowing ordinary tablets or capsules, and can also be improved by adding sweeteners to improve the taste.…”

Preventive and therapeutic effects of natural products and herbal extracts on nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

“…A randomized controlled trial of 191 patients with NASH revealed that betaine supplementation for 8 weeks reduced hepatic steatosis by 25%, and liver biopsy after 12 months of treatment confirmed that betaine prevented worsening of steatosis in 55 patients with NASH (Chen et al, 2016). Betaine treatment of high‐fat diet‐induced ApoE−/− mice resulted in a significant reduction in white fat; HFD‐fed mice showed a significant reduction in the adipogenic genes PPARγ and CD36 (Li, Jiang, et al, 2022). In a mouse model of NAFLD, betaine significantly increased AMPK expression while inhibiting downstream lipid synthesis related genes; it also increased FGF10 secretion and decreased CPT1A protein expression—thus preventing NAFLD by reducing lipid synthesis and improving fatty acid oxidation (Chen, Zhang, et al, 2021).…”