Adenylyl cyclase type 5 deficiency protects against diet-induced obesity and insulin resistance

David Ho, Xin Zhao, Lin Yan, Chujun Yuan, Haihong Zong, Dorothy E. Vatner, Jeffrey E. Pessin, Stephen F. Vatner

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Adenylyl cyclase type 5 knockout (AC5KO) mice have increased longevity and share a similar phenotype with calorie-restricted wild-type (WT) mice. To determine the in vivo metabolic properties of AC5 deficiency, we compared the effects of standard diet (SD) and high-fat diet (HFD) on obesity, energy balance, glucose regulation, and insulin sensitivity. AC5KO mice on SD had reduced body weight and adiposity compared with WT mice. Blood cholesterol and triglyceride levels were also significantly reduced in AC5KO mice. Indirect calorimetry demonstrated increased oxygen consumption, respiratory exchange ratio, and energy expenditure in AC5KO compared with WT mice on both SD and HFD. AC5KO mice also displayed improved glucose tolerance and increased whole-body insulin sensitivity, accompanied by decreased liver glycogen stores. Euglycemic-hyperinsulinemic clamp studies confirmed the marked improvement of glucose homeostasis and insulin sensitivity in AC5KO mice primarily through increased insulin sensitivity in skeletal muscle. Moreover, the genes involved in mitochondrial biogenesis and function were significantly increased in AC5KO skeletal muscle. These data demonstrate that deficiency of AC5 protects against obesity, glucose intolerance, and insulin resistance, supporting AC5 as a potential novel therapeutic target for treatment of obesity and diabetes.

Original languageEnglish (US)
Pages (from-to)2636-2645
Number of pages10
JournalDiabetes
Volume64
Issue number7
DOIs
StatePublished - Jul 1 2015

Fingerprint

Insulin Resistance
Obesity
Knockout Mice
Diet
High Fat Diet
Glucose
Skeletal Muscle
Indirect Calorimetry
Liver Glycogen
Glucose Clamp Technique
Glucose Intolerance
Adiposity
Organelle Biogenesis
adenylyl cyclase type V
Oxygen Consumption
Energy Metabolism
Triglycerides
Homeostasis
Cholesterol
Body Weight

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Ho, D., Zhao, X., Yan, L., Yuan, C., Zong, H., Vatner, D. E., ... Vatner, S. F. (2015). Adenylyl cyclase type 5 deficiency protects against diet-induced obesity and insulin resistance. Diabetes, 64(7), 2636-2645. https://doi.org/10.2337/db14-0494

Adenylyl cyclase type 5 deficiency protects against diet-induced obesity and insulin resistance. / Ho, David; Zhao, Xin; Yan, Lin; Yuan, Chujun; Zong, Haihong; Vatner, Dorothy E.; Pessin, Jeffrey E.; Vatner, Stephen F.

In: Diabetes, Vol. 64, No. 7, 01.07.2015, p. 2636-2645.

Research output: Contribution to journalArticle

Ho, David ; Zhao, Xin ; Yan, Lin ; Yuan, Chujun ; Zong, Haihong ; Vatner, Dorothy E. ; Pessin, Jeffrey E. ; Vatner, Stephen F. / Adenylyl cyclase type 5 deficiency protects against diet-induced obesity and insulin resistance. In: Diabetes. 2015 ; Vol. 64, No. 7. pp. 2636-2645.
@article{2579f3fa1de840028fa867a66cf1c232,
title = "Adenylyl cyclase type 5 deficiency protects against diet-induced obesity and insulin resistance",
abstract = "Adenylyl cyclase type 5 knockout (AC5KO) mice have increased longevity and share a similar phenotype with calorie-restricted wild-type (WT) mice. To determine the in vivo metabolic properties of AC5 deficiency, we compared the effects of standard diet (SD) and high-fat diet (HFD) on obesity, energy balance, glucose regulation, and insulin sensitivity. AC5KO mice on SD had reduced body weight and adiposity compared with WT mice. Blood cholesterol and triglyceride levels were also significantly reduced in AC5KO mice. Indirect calorimetry demonstrated increased oxygen consumption, respiratory exchange ratio, and energy expenditure in AC5KO compared with WT mice on both SD and HFD. AC5KO mice also displayed improved glucose tolerance and increased whole-body insulin sensitivity, accompanied by decreased liver glycogen stores. Euglycemic-hyperinsulinemic clamp studies confirmed the marked improvement of glucose homeostasis and insulin sensitivity in AC5KO mice primarily through increased insulin sensitivity in skeletal muscle. Moreover, the genes involved in mitochondrial biogenesis and function were significantly increased in AC5KO skeletal muscle. These data demonstrate that deficiency of AC5 protects against obesity, glucose intolerance, and insulin resistance, supporting AC5 as a potential novel therapeutic target for treatment of obesity and diabetes.",
author = "David Ho and Xin Zhao and Lin Yan and Chujun Yuan and Haihong Zong and Vatner, {Dorothy E.} and Pessin, {Jeffrey E.} and Vatner, {Stephen F.}",
year = "2015",
month = "7",
day = "1",
doi = "10.2337/db14-0494",
language = "English (US)",
volume = "64",
pages = "2636--2645",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "7",

}

TY - JOUR

T1 - Adenylyl cyclase type 5 deficiency protects against diet-induced obesity and insulin resistance

AU - Ho, David

AU - Zhao, Xin

AU - Yan, Lin

AU - Yuan, Chujun

AU - Zong, Haihong

AU - Vatner, Dorothy E.

AU - Pessin, Jeffrey E.

AU - Vatner, Stephen F.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Adenylyl cyclase type 5 knockout (AC5KO) mice have increased longevity and share a similar phenotype with calorie-restricted wild-type (WT) mice. To determine the in vivo metabolic properties of AC5 deficiency, we compared the effects of standard diet (SD) and high-fat diet (HFD) on obesity, energy balance, glucose regulation, and insulin sensitivity. AC5KO mice on SD had reduced body weight and adiposity compared with WT mice. Blood cholesterol and triglyceride levels were also significantly reduced in AC5KO mice. Indirect calorimetry demonstrated increased oxygen consumption, respiratory exchange ratio, and energy expenditure in AC5KO compared with WT mice on both SD and HFD. AC5KO mice also displayed improved glucose tolerance and increased whole-body insulin sensitivity, accompanied by decreased liver glycogen stores. Euglycemic-hyperinsulinemic clamp studies confirmed the marked improvement of glucose homeostasis and insulin sensitivity in AC5KO mice primarily through increased insulin sensitivity in skeletal muscle. Moreover, the genes involved in mitochondrial biogenesis and function were significantly increased in AC5KO skeletal muscle. These data demonstrate that deficiency of AC5 protects against obesity, glucose intolerance, and insulin resistance, supporting AC5 as a potential novel therapeutic target for treatment of obesity and diabetes.

AB - Adenylyl cyclase type 5 knockout (AC5KO) mice have increased longevity and share a similar phenotype with calorie-restricted wild-type (WT) mice. To determine the in vivo metabolic properties of AC5 deficiency, we compared the effects of standard diet (SD) and high-fat diet (HFD) on obesity, energy balance, glucose regulation, and insulin sensitivity. AC5KO mice on SD had reduced body weight and adiposity compared with WT mice. Blood cholesterol and triglyceride levels were also significantly reduced in AC5KO mice. Indirect calorimetry demonstrated increased oxygen consumption, respiratory exchange ratio, and energy expenditure in AC5KO compared with WT mice on both SD and HFD. AC5KO mice also displayed improved glucose tolerance and increased whole-body insulin sensitivity, accompanied by decreased liver glycogen stores. Euglycemic-hyperinsulinemic clamp studies confirmed the marked improvement of glucose homeostasis and insulin sensitivity in AC5KO mice primarily through increased insulin sensitivity in skeletal muscle. Moreover, the genes involved in mitochondrial biogenesis and function were significantly increased in AC5KO skeletal muscle. These data demonstrate that deficiency of AC5 protects against obesity, glucose intolerance, and insulin resistance, supporting AC5 as a potential novel therapeutic target for treatment of obesity and diabetes.

UR - http://www.scopus.com/inward/record.url?scp=84962127828&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962127828&partnerID=8YFLogxK

U2 - 10.2337/db14-0494

DO - 10.2337/db14-0494

M3 - Article

VL - 64

SP - 2636

EP - 2645

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 7

ER -