CTRP7 deletion attenuates obesity-linked glucose intolerance, adipose tissue inflammation, and hepatic stress

Pia S. Petersen, Xia Lei, Risa Wolf, Susana Rodriguez, Stefanie Y. Tan, Hannah C. Little, Michael A Schweitzer, Thomas Magnuson, Kimberley Steele, Guang William Wong

Research output: Contribution to journalArticle

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/TNFrelated 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 of CTRP7 in liver was also significantly upregulated in obese humans and positively correlated with gluconeogenic genes. In mice, Ctrp7 expression 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.

Original languageEnglish (US)
Pages (from-to)E309-E325
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume312
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Glucose Intolerance
Adipose Tissue
Obesity
Inflammation
Liver
Proteins
Glucose
Insulin Resistance
Obese Mice
Protein Deficiency
Fat-Restricted Diet
Endoplasmic Reticulum Stress
High Fat Diet
Liver Cirrhosis
Fasting
Hemoglobins
Triglycerides
Body Mass Index
Homeostasis
Body Weight

Keywords

  • Adipokine
  • Diabetes
  • Inflammation
  • Insulin resistance
  • Obesity
  • Oxidative and endoplasmic reticulum stress

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

CTRP7 deletion attenuates obesity-linked glucose intolerance, adipose tissue inflammation, and hepatic stress. / Petersen, Pia S.; Lei, Xia; Wolf, Risa; Rodriguez, Susana; Tan, Stefanie Y.; Little, Hannah C.; Schweitzer, Michael A; Magnuson, Thomas; Steele, Kimberley; Wong, Guang William.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 312, No. 4, 01.04.2017, p. E309-E325.

Research output: Contribution to journalArticle

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