Genetic vulnerability to diet-induced obesity in the C57BL/6J mouse: physiological and molecular characteristics

doi:10.1016/j.physbeh.2004.02.006

Physiology & Behavior

Volume 81, Issue 2, April 2004, Pages 243-248

https://doi.org/10.1016/j.physbeh.2004.02.006 Get rights and content

Abstract

The development of the metabolic syndrome in an increasing percentage of the populations of Western societies, particularly in the United States, requires valid models for establishing basic biochemical changes and performing preclinical studies on potential drug targets. The C57BL/6J mouse has become an important model for understanidng the interplay between genetic background and environmental challenges such as high-fat/high-calorie diets that predispose to the development of the metabolic syndrome. This review highlights metabolic and signal transduction features that are altered during the course of disease progression, many of which mirror the human situation.

Introduction

In 1988, Reaven [1] described the existence of a constellation of metabolic abnormalities that seemed to occur together and be related to the etiology of cardiovascular disease. He termed this clustering of anomalies syndrome X. Syndrome X was defined as the coexistence of hyperinsulinemia, hyperlipidemia, and hypertension in nondiabetic individuals. Together, these features were seen as a risk factor for both cardiovascular disease and Type 2 diabetes. Later, intra-abdominal obesity was added as a risk factor, and Bjorntorp [2] suggested the term metabolic syndrome. More recent research has shown that increased fasting insulin, increased fasting glucose, and elevations in hemoglobin A_1c (HbA_1c) all predict both the development of Type 2 diabetes and cardiovascular disease. Bjorntorp suggested that the “metabolic syndrome” be called the “civilization syndrome” because the various metabolic components of the syndrome as well as clinical diabetes have been seen to be associated with lifestyle changes associated with Western urbanization. These changes include the increased mechanization of work formerly done by humans as physical activity, increased accessibility and affordability of dense, high-calorie foods, and urban sprawl that increasingly necessitates automobile use instead of walking. In addition to decreased exercise and increased caloric intake, epidemiological observations provide evidence that the development of insulin resistance and Type 2 diabetes is related to fat consumption and negatively related to carbohydrate consumption. To understand the molecular aspects that link these metabolic features, it is important to have appropriate animal models. One of these models that is gaining increasing attention is the C57BL/6J (B6) mouse.

Section snippets

Diet-induced obesity in B6 mice

An increase in dietary fat content has been shown to produce diabetes and obesity in various strains of mice [3], [4] and in rats [5]. The B6 mouse is a particularly good model of the human metabolic syndrome because it develops a syndrome of obesity, hyperinsulinemia, hyperglycemia, and hypertension, when allowed ad libitum access to a high-fat diet [4], but remains lean and physically normal when restricted to low-fat chow. In marked comparison to B6, other strains, such as the A/J mouse or

Catecholamine signaling and control of adipose tissue metabolism

The sympathetic nervous system plays an integral role in regulating both energy intake and energy expenditure in most mammals. Catecholamines increase lipolysis and decrease triglyceride-rich lipoprotein accumulation in WAT while, at the same time, increasing thermogenesis in BAT, thereby resulting in an overall decrease in total body fat stores [20], [21], [22]. The actions of these catecholamines occur via the β-adrenergic receptors (βARs), members of the G-protein-coupled receptor family.

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Genetic vulnerability to diet-induced obesity in the C57BL/6J mouse: physiological and molecular characteristics

Abstract

Introduction

Section snippets

Diet-induced obesity in B6 mice

Catecholamine signaling and control of adipose tissue metabolism

Metabolism

Metabolism

Atherosclerosis

Am. J. Clin. Nutr.

Physiol. Behav.

Metabolism

Metabolism

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

FEBS Lett.

J. Biol. Chem.

Metabolism

Banting lecture 1988. Role of insulin resistance in human disease

Diabetes

Abdominal fat distribution and the metabolic syndrome

J. Cardiovasc. Pharmacol.

Dietary obesity in nine inbred mouse strains

Am. J. Physiol.

Diet-induced type II diabetes in C57BL/6J mice

Diabetes

Dietary obesity in rats: body weight and body fat accretion in seven strains of rats

J. Nutr.

Diet-induced changes in uncoupling proteins in obesity-prone and obesity-resistant strains of mice

Proc. Natl. Acad. Sci. U. S. A.

Influence of nutritional factors on prevalence of diabetes

Diabetes

High-fat diets and the immune response of C57Bl mice

Br. J. Nutr.

Locomotor activity of various types of genetically obese mice

Proc. Soc. Exp. Biol. Med.

Low plasma leptin in response to dietary fat in diabetes- and obesity-prone mice

Diabetes