title: CTRP7 deletion attenuates obesity-linked glucose intolerance, adipose tissue inflammation, and hepatic stress.
abstract: Chronic low-grade inflammation and cellular stress are important contributors to obesity-linked metabolic dysfunction. Here, we uncover an immune-metabolic role for C1q/TNF-related protein 7 (CTRP7), a secretory protein of the C1q family with previously unknown function. In obese humans, circulating CTRP7 levels were markedly elevated and positively correlated with body mass index, glucose, insulin, insulin resistance index, hemoglobin A1c, and triglyceride levels. Expression ofCTRP7in liver was also significantly upregulated in obese humans and positively correlated with gluconeogenic genes. In mice,Ctrp7expression was differentially modulated in various tissues by fasting and refeeding and by diet-induced obesity. A genetic loss-of-function mouse model was used to determine the requirement of CTRP7 for metabolic homeostasis. When fed a control low-fat diet, male or female mice lacking CTRP7 were indistinguishable from wild-type littermates. In obese male mice consuming a high-fat diet, however, CTRP7 deficiency attenuated insulin resistance and enhanced glucose tolerance, effects that were independent of body weight, metabolic rate, and physical activity level. Improved glucose metabolism in CTRP7-deficient mice was associated with reduced adipose tissue inflammation, as well as decreased liver fibrosis and cellular oxidative and endoplasmic reticulum stress. These results provide a link between elevated CTRP7 levels and impaired glucose metabolism, frequently associated with obesity. Inhibiting CTRP7 action may confer beneficial metabolic outcomes in the setting of obesity and diabetes.
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Pia S
authors.initials: PS
authors.lastname: Petersen
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Xia
authors.initials: X
authors.lastname: Lei
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
authors.forename: Risa M
authors.initials: RM
authors.lastname: Wolf
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Susana
authors.initials: S
authors.lastname: Rodriguez
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Stefanie Y
authors.initials: SY
authors.lastname: Tan
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Little
authors.affiliation: Department of Surgery, Johns Hopkins Center for Bariatric Surgery, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schweitzer
authors.affiliation: Department of Surgery, Johns Hopkins Center for Bariatric Surgery, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Magnuson
authors.affiliation: Department of Surgery, Johns Hopkins Center for Bariatric Surgery, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.
authors.forename: Kimberley E
authors.initials: KE
authors.lastname: Steele
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland; gwwong@jhmi.edu.|Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: G William
authors.initials: GW
authors.lastname: Wong
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D018149:Glucose Intolerance / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: adipokine; diabetes; inflammation; insulin resistance; obesity; oxidative and endoplasmic reticulum stress