Betaine alleviates obesity-related metabolic disorders in rats: insights from microbiomes, lipidomics, and transcriptomics

Xian Wang¹Xin Shang²Yan Pan¹Yu Fu¹Zhu Hui Lian^3*Shuxun Yan^1*

• ¹First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
• ²First Clinical Medical College, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan Province, China
• ³Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Sun Yat-sen University, Guangzhou, Guangdong Province, China

Betaine is a natural food component that plays an important role in improving body composition, but the details of its effects on adipose tissue remains to be elucidated. Here, we hypothesize that betaine can alleviate obesity-related metabolic disorders, thus gut microbiota, transcriptomics and lipidomics were used to investigate the obesity-alleviating effects of betaine on high-fat diet (HFD)-fed rats. Our findings imply that the supplementation of betaine can diminish the accumulation of lipid in visceral adipose tissue, thereby improving dyslipidemia and leptin resistance. Additionally, betaine has been linked to the alleviation of community alterations in gut microbiota resulting from HFD, facilitating the proliferation of beneficial microbiota (e.g., Lactobacillu, Lachnospiraceae_NK4A136_group) and the generation of short-chain fatty acids (SCFA). Particularly, our results indicate that betaine treatment led to notable variations in the content of DHA-riched glycerophospholipids which exhibited a positive correlation with the secretion of intestinal hormone (e.g., cholecystokininand peptide YY). Additionally, betaine up-regulated the expression of genes related to thermogenesis and glycerophospholipids metabolic pathways in the adipose tissues. These results highlight that betaine has the effect of promoting lipolysis, and provide a basis for developing betaine as a candidate for antiobesity therapy in the future. 1 Deleted: The objective of this research was to investigate the effect 80 of betaine on the prevention of obesity and associated metabolic 81 disorders, as well as the mechanisms involved, in rats. Our findings 82 indicate that betaine has the potential to decrease obesity and its 83 associated dyslipidemia by regulating adipose tissue metabolism and 84 promote the synthesis of polyunsaturated phospholipid rich in 85 docosahexaenoic acid (DHA). The underlying mechanism of betaine 86 action might encompass its influence on gut microbiota modulation 87 and SCFA metabolism.