title: MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids.
abstract: Type 2 diabetes (T2D) is characterized by insulin resistance and increased hepatic glucose production, yet the molecular mechanisms underlying these abnormalities are poorly understood. MicroRNAs (miRs) are a class of small, noncoding RNAs that have been implicated in the regulation of human diseases, including T2D. miR-26a is known to play a critical role in tumorigenesis; however, its function in cellular metabolism remains unknown. Here, we determined that miR-26a regulates insulin signaling and metabolism of glucose and lipids. Compared with lean individuals, overweight humans had decreased expression of miR-26a in the liver. Moreover, miR-26 was downregulated in 2 obese mouse models compared with control animals. Global or liver-specific overexpression of miR-26a in mice fed a high-fat diet improved insulin sensitivity, decreased hepatic glucose production, and decreased fatty acid synthesis, thereby preventing obesity-induced metabolic complications. Conversely, silencing of endogenous miR-26a in conventional diet-fed mice impaired insulin sensitivity, enhanced glucose production, and increased fatty acid synthesis. miR-26a targeted several key regulators of hepatic metabolism and insulin signaling. These findings reveal miR-26a as a regulator of liver metabolism and suggest miR-26a should be further explored as a potential target for the treatment of T2D.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Fu
authors.forename: Bingning
authors.initials: B
authors.lastname: Dong
authors.forename: Yan
authors.initials: Y
authors.lastname: Tian
authors.forename: Philippe
authors.initials: P
authors.lastname: Lefebvre
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Meng
authors.forename: Xichun
authors.initials: X
authors.lastname: Wang
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Lou
authors.forename: Richard
authors.initials: R
authors.lastname: Jove
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: David D
authors.initials: DD
authors.lastname: Moore
authors.forename: Wendong
authors.initials: W
authors.lastname: Huang
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D005947:Glucose; D007328:Insulin; D035683:MicroRNAs; C528163:MIRN26 microRNA, human; C543693:Mirn26 microRNA, mouse