title: PAQR3 has modulatory roles in obesity, energy metabolism, and leptin signaling.
abstract: Diet-induced obesity is commonly associated with leptin resistance, and attenuated leptin signaling contributes to the progression of obesity. PAQR3 is a member of the progesterone and AdipoQ receptor (PAQR) family with close homology to adiponectin receptors. We hypothesized that PAQR3 is implicated in the regulation of obesity and energy homeostasis. To address this hypothesis, we fed Paqr3-deleted mice with high-fat diet (HFD), followed by analyses to evaluate obesity, hepatic steatosis, insulin resistance, metabolic rate, and leptin signaling. We found that mice with deletion of Paqr3 are resistant to HFD-induced obesity and hepatic steatosis, accompanied by improvement of insulin resistance and insulin signaling. Paqr3-deleted mice have an increased energy expenditure and physical activity. HFD-induced leptin resistance is reversed by Paqr3 ablation. Overexpression of PAQR3 reduces leptin signaling whereas deletion of Paqr3 enhances leptin signaling in the hypothalamus. In conclusion, this study reveals that PAQR3 has an important physiological function in modulating obesity, energy metabolism, and leptin signaling.
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China. ychen3@sibs.ac.cn.
authors.forename: Lingdi
authors.initials: L
authors.lastname: Wang
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Zhenghu
authors.initials: Z
authors.lastname: Li
authors.forename: Tingting
authors.initials: T
authors.lastname: Xia
authors.forename: Lu
authors.initials: L
authors.lastname: Zhu
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Yongxian
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Feifan
authors.initials: F
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D000906:Antibodies; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000906:Antibodies; D004041:Dietary Fats; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D008565:Membrane Proteins; C523677:RKTG protein, mouse