Betaine prevented high-fat diet-induced NAFLD by regulating the FGF10/AMPK signaling pathway in ApoE−/− mice

Chen, Weiqiang; Zhang, Xiaoli; Xu, Minwen; Jiang, Lixia; Zhou, Min; Liu, Wenjun; Chen, Zhijun; Wang, Yucai; Qing-yan, Zou; Wang, Liefeng

doi:10.1007/s00394-020-02362-6

Cited by 41 publications

(27 citation statements)

References 35 publications

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“…The results of the present study also showed that supplementation significantly decreased the concentration of TG and TCHOL in serum, which was similar to the results reported by Chen et al. (2018, 2020 ) as well as Zhang et al. (2019) .…”

Section: Discussionsupporting

confidence: 92%

Dietary supplementation of betaine promotes lipolysis by regulating fatty acid metabolism in geese

Yang

Sosa-Montes

et al. 2021

Poultry Science

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Supplementation of betaine in the diet appears to regulate fatty acid metabolism and decrease fat deposition. This study aims to identify the effects of dietary supplementation of betaine on zootechnical performance, fatty acid synthesis, abdominal fat deposition, and morphology. Three hundred healthy, male, one-day-old Jiangnan White geese of similar body weight were randomly divided into 5 groups, with 6 replicates per treatment and 10 geese per replicate, and given the following amounts of supplementary betaine: 0 (group A), 600 mg/kg (group B), 1,200 mg/kg (group C), 1,800 mg/kg (group D), or 2,400 mg/kg (group E). Feed intake ( FI ), body weight ( BW ), abdominal fat and sebum thickness, clinical blood parameters, hepatic enzyme activity, and abdominal fat morphology were monitored during the experiment. All geese had free access to feed and water throughout the study. Our results indicate that supplementation of betaine increased zootechnical performance at 21 and 42 d of age. The percentage of abdominal fat and sebum thickness of geese at 63 d of age decreased linearly with the addition of betaine ( P < 0.05). The triglyceride ( TG ) and total cholesterol ( TCHOL ) content of serum decreased with the increased level of betaine when measured at 63 d of age ( P <0.05). Hormone sensitive lipase ( HSL ) increased with the level of betaine ( P <0.05). However, dietary betaine appeared to decrease the activity of fatty acid synthase ( FAS ) in the geese at 42 d and 63 d of age ( P <0.05). The percentage of total area of lipid droplet decreased with the increased level of betaine supplementation. In conclusion, dietary supplementation of betaine increased lipolysis and decreased fat deposition in the finishing period of geese via reducing feed intake. However, the precise mode-of–action is yet unclear and warrants further research.

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Section: Discussionsupporting

confidence: 92%

Dietary supplementation of betaine promotes lipolysis by regulating fatty acid metabolism in geese

Yang

Sosa-Montes

et al. 2021

Poultry Science

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“…Further, betaine supplementation decreased hepatic lipid accumulation by slowing lipogenesis and enhancing lipophagy in ApoE−/− mouse models through enhanced expression of PPARα and elevated fatty acid oxidation by upregulating expression of mitochondrial and extra-mitochondrial fatty acid oxidation enzymes [ 158 ]. In addition, betaine increased AMPK, fibroblast growth factor 10, and adipose triglyceride lipase levels while suppressing lipid-metabolism-related genes in ApoE−/− mice fed a high-fat diet [ 159 ]. Mice fed a high-sucrose diet also exhibit significant fat accumulation and increased lipogenic activity in the liver similar to what was seen in high-fat diet administration, which were attenuated with betaine treatment via upregulation of AMPK [ 160 ].…”

Section: Disease Prevention By Betaine Administrationmentioning

confidence: 99%

Beneficial Effects of Betaine: A Comprehensive Review

Arumugam

Paal

Donohue

et al. 2021

Biology

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Medicinal herbs and many food ingredients possess favorable biological properties that contribute to their therapeutic activities. One such natural product is betaine, a stable, nontoxic natural substance that is present in animals, plants, and microorganisms. Betaine is also endogenously synthesized through the metabolism of choline or exogenously consumed through dietary intake. Betaine mainly functions as (i) an osmolyte and (ii) a methyl-group donor. This review describes the major physiological effects of betaine in whole-body health and its ability to protect against both liver- as well as non-liver-related diseases and conditions. Betaine’s role in preventing/attenuating both alcohol-induced and metabolic-associated liver diseases has been well studied and is extensively reviewed here. Several studies show that betaine protects against the development of alcohol-induced hepatic steatosis, apoptosis, and accumulation of damaged proteins. Additionally, it can significantly prevent/attenuate progressive liver injury by preserving gut integrity and adipose function. The protective effects are primarily associated with the regulation of methionine metabolism through removing homocysteine and maintaining cellular SAM:SAH ratios. Similarly, betaine prevents metabolic-associated fatty liver disease and its progression. In addition, betaine has a neuroprotective role, preserves myocardial function, and prevents pancreatic steatosis. Betaine also attenuates oxidant stress, endoplasmic reticulum stress, inflammation, and cancer development. To conclude, betaine exerts significant therapeutic and biological effects that are potentially beneficial for alleviating a diverse number of human diseases and conditions.

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“…The HFD (NAFLD) group was fed a high fat diet (45% kcal fat; MD12032; Jiangsu Medicience Ltd., Jiangsu, China). The HB (NAFLD + Betaine) group was fed a high fat diet with betaine in drinking water (2% w/v; Beijing Solarbio Science & Technology Co., Ltd., Beijing, China) [19,34]. The mice were sampled in they were 25 weeks old.…”

Section: Animal and Dietmentioning

confidence: 99%

“…Betaine (N,N,N-trimethylglycine, glycine betaine) exists in various common foods，including beets, spinach, chinese wolfberry, wheat, shrimp and shellfish [15][16][17]. Betaine has been widely used for decades due to its anti-inflammatory, methyl donor, and osmotic pressure regulator effects [18] and has been proven to effectively improve NAFLD [19][20][21][22][23][24]. As reported, betaine prevented high fat diet-induced NAFLD by regulating the FGF10/AMPK signaling pathway in ApoE -/mice [19].…”

Section: Introductionmentioning

confidence: 99%

“…Betaine has been widely used for decades due to its anti-inflammatory, methyl donor, and osmotic pressure regulator effects [18] and has been proven to effectively improve NAFLD [19][20][21][22][23][24]. As reported, betaine prevented high fat diet-induced NAFLD by regulating the FGF10/AMPK signaling pathway in ApoE -/mice [19]. Supplementing betaine after high fat diet-induced NAFLD will make the downstream pathways, which are involved in insulin signal transduction, gluconeogenesis and glycogen synthesis, function normally and improve insulin resistance and steatosis [20].…”

Section: Introductionmentioning

confidence: 99%

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Transcriptome and translatome analyses reveal the regulatory role of betaine in high fat diet (HFD)-induced hepatic steatosis

Huang

Luo

et al. 2021

Preprint

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Non-alcoholic fatty liver disease (NAFLD) is a common disease with a multitude of complications. Increasing evidence shows that the dietary supplement with betaine, a natural chemical molecule, can effectively reduce the fat accumulation in the liver. Translational regulation is considered to play a vital role in gene expression, but whether betaine functions through the regulation of gene translational level is still unclear. To this end, RNC-seq (ribosome-nascent chain complex bound mRNA sequencing) and RNA-seq co-analyses were performed to identify betaine target genes by using the liver samples from high-fat diet + betaine treated and high-fat diet treated mice. The results showed that betaine does play a lipid-lowering role by regulating the expression of gene translation levels; some NAFLD- and lipid metabolism- associated genes were differentially expressed at translational level, for example. And the mRNA translation ratio (TR) of gene significantly increased after betaine treatment. Besides, it is found that the regulation of some genes at transcriptional level is opposite to that at translational level, which indicates that transcriptional regulation and translational regulation may be independent from each other. Finally, we identified several candidate genes, especially Gpc1 , which may mediate the lipid-lowering effect of betaine in the liver. To sum up, this study depicted the molecular portrait of mice liver with or without betaine treatment from the angel of translatome and transcriptome, giving insights into the molecular mechanism of betaine-mediated lipid-lowering effect and also providing new clues for understanding and prevention of NAFLD.

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Betaine prevented high-fat diet-induced NAFLD by regulating the FGF10/AMPK signaling pathway in ApoE−/− mice

Cited by 41 publications

References 35 publications

Dietary supplementation of betaine promotes lipolysis by regulating fatty acid metabolism in geese

Dietary supplementation of betaine promotes lipolysis by regulating fatty acid metabolism in geese

Beneficial Effects of Betaine: A Comprehensive Review

Transcriptome and translatome analyses reveal the regulatory role of betaine in high fat diet (HFD)-induced hepatic steatosis

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