title: The beneficial effects of betaine on dysfunctional adipose tissue and N6-methyladenosine mRNA methylation requires the AMP-activated protein kinase α1 subunit.
abstract: The current study was conducted to determine whether betaine could improve fatty acid oxidation, mitochondrial function and N6-methyladenosine (m(6)A) mRNA methylation in adipose tissue in high-fat-induced mice and how AMP-activated protein kinase α1 subunit (AMPKα1) was involved. AMPKα1 knockout mice and wild-type mice were fed either a low-fat diet, high-fat diet or high-fat diet supplemented with betaine in the drinking water for 8weeks. Our results showed that mitochondrial genes (PGC1α) and β-oxidation-related genes (CPT1a) at protein level were increased in wild-type mice supplemented with betaine when compared with those in mice with high-fat diet. Betaine also decreased FTO expression and improved m(6)A methylation in adipose tissue of wild-type mice with high-fat diet. However, betaine failed to exert the abovementioned effects in AMPKα1 knockout mice. In adipocytes isolated from mice with high-fat diet, betaine treatment increased lipolysis and lipid oxidation. Moreover, betaine decreased FTO expression and increased m(6)A methylation. However, while AMPKα1 was knockdown, no remarkable changes in adipocytes were observed under betaine treatment. Our results indicated that betaine supplementation rectified mRNA hypomethylation and high FTO expression induced by high-fat diet, which may contribute to its beneficial effects on impaired adipose tissue function. Our results suggested that the AMPKα1 subunit is required for the beneficial effects of betaine on dysfunctional adipose tissue and m(6)A methylation. These results may provide the foundation for a mechanism that links m(6)A methylation status in RNA, AMPKα1 phosphorylation and dysfunctional adipose tissue induced by high-fat diet.
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture, Zhejiang Provincial Laboratory of Feed and Animal Nutrition, Institute of Feed Science, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. China; Institute of Subtropical Agriculture, The Chinese Academy of Science, Changsha, Hunan 410125, P. R. China.
authors.forename: Xihong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture, Zhejiang Provincial Laboratory of Feed and Animal Nutrition, Institute of Feed Science, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. China.
authors.forename: Jingqing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture, Zhejiang Provincial Laboratory of Feed and Animal Nutrition, Institute of Feed Science, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture, Zhejiang Provincial Laboratory of Feed and Animal Nutrition, Institute of Feed Science, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. China.
authors.forename: Weiche
authors.initials: W
authors.lastname: Wu
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture, Zhejiang Provincial Laboratory of Feed and Animal Nutrition, Institute of Feed Science, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. China.
authors.forename: Xinxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture, Zhejiang Provincial Laboratory of Feed and Animal Nutrition, Institute of Feed Science, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. China. Electronic address: yzwang321@zju.edu.cn.
authors.forename: Yizhen
authors.initials: Y
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001622:Betaine / Q000737:chemistry*; D001835:Body Weight; D019175:DNA Methylation; D059305:Diet, High-Fat; D005765:Gastrointestinal Agents / Q000737:chemistry; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D005765:Gastrointestinal Agents; D007328:Insulin; D012333:RNA, Messenger; D001622:Betaine; C010223:N-methyladenosine; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases; D000241:Adenosine
keywords: AMP-activated protein kinase; Adipose tissue; Betaine; Fatty acid oxidation; N6-methyladenosine methylation