title: Adipose-specific deletion ofKif5bexacerbates obesity and insulin resistance in a mouse model of diet-induced obesity.
abstract: Recent studies have shown that KIF5B (conventional kinesin heavy chain) mediates glucose transporter type 4 translocation and adiponectin secretion in 3T3-L1 adipocytes, suggesting an involvement of KIF5B in the homeostasis of metabolism. However, thein vivophysiologic function of KIF5B in adipose tissue remains to be determined. In this study, adipose-specificKif5bknockout (F-K5bKO) mice were generated using the Cre-LoxP strategy. F-K5bKO mice had similar body weights to controls fed on a standard chow diet. However, F-K5bKO mice had hyperlipidemia and significant glucose intolerance and insulin resistance. Deletion ofKif5baggravated the deleterious impact of a high-fat diet (HFD) on body weight gain, hepatosteatosis, glucose tolerance, and systematic insulin sensitivity. These changes were accompanied by impaired insulin signaling, decreased secretion of adiponectin, and increased serum levels of leptin and proinflammatory adipokines. F-K5bKO mice fed on an HFD exhibited lower energy expenditure and thermogenic dysfunction as a result of whitening of brown adipose due to decreased mitochondria biogenesis and down-regulation of key thermogenic gene expression. In conclusion, selective deletion ofKif5bin adipose tissue exacerbates HFD-induced obesity and its associated metabolic disorders, partly through a decrease in energy expenditure, dysregulation of adipokine secretion, and insulin signaling.-Cui, J., Pang, J., Lin, Y.-J., Gong, H., Wang, Z.-H., Li, Y.-X., Li, J., Wang, Z., Jiang, P., Dai, D.-P., Li, J., Cai, J.-P., Huang, J.-D., Zhang, T.-M. Adipose-specific deletion ofKif5bexacerbates obesity and insulin resistance in a mouse model of diet-induced obesity.
authors.affiliation: The Ministry of Health (MOH) Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Cui
authors.affiliation: The Ministry of Health (MOH) Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Pang
authors.affiliation: The Ministry of Health (MOH) Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: The Ministry of Health (MOH) Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Gong
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou, China.
authors.forename: Zhen-He
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou, China.
authors.forename: Yun-Xuan
authors.initials: YX
authors.lastname: Li
authors.affiliation: The Ministry of Health (MOH) Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Zai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: The Ministry of Health (MOH) Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.affiliation: The Ministry of Health (MOH) Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
authors.forename: Da-Peng
authors.initials: DP
authors.lastname: Dai
authors.affiliation: The Ministry of Health (MOH) Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: The Ministry of Health (MOH) Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Cai
authors.affiliation: School of Biomedical Sciences, University of Hong Kong, Hong Kong, China; jdhuang@hku.hk.|Shenzhen Institute of Research and Innovation, University of Hong Kong, Hong Kong, China.|The Centre for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Shenzhen, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Huang
authors.affiliation: The Ministry of Health (MOH) Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China; tmzhang126@126.com.
authors.forename: Tie-Mei
authors.initials: TM
authors.lastname: Zhang
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D018149:Glucose Intolerance; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced*
chemical_list: C475469:Kif5b protein, mouse; D016547:Kinesins
keywords: adipogenesis and lipolysis; adipokine; motor protein; thermogenesis