**1. Introduction**

The number of obese patients is rapidly increasing, due to the change of lifestyle, such as eating habits of high calorie-diet and sedentary life. Obesity and the obesity-related diseases, such as diabetes mellitus, dyslipidemia, and hypertension, are risk factors for several severe diseases, including cardiovascular disease and cancer, and deteriorate the quality of life (QOL) of patients and result in high medical expenses [1, 2]. Moreover, nonalcoholic fatty liver disease (NAFLD) is recently well recognized as the most common chronic liver disease, and the NAFLD is strongly associated with obesity and the related diseases [3, 4]. In Western countries, 4–22% of NAFLD patients lead to hepatocellular cartinoma [5]. Metabolic abnormalities based on obesity, such as hyperinsulinemia, dyslipidemia, and ectopic lipid accumulation, induce the various complications including microangiopathy and nonalcoholic steatohepatitis (NASH).

Obesity is considered to be caused by an imbalance in individual energy, and energy homeostasis in body is maintained by a balance between energy intake and energy expenditure. When the former exceeds the latter, overt energy is accumulated in adipose tissue and resulting in

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

obesity [6]. The basic therapies for obesity are appropriate dietary restriction for the purpose of decreasing energy intake and effective exercise for the purpose of promoting energy expenditure. The life style modifications, such as diet therapy and exercise, mainly occupy the treatments for obesity; however, medical therapy is performed on patients who do not show weight loss effect by the life style modifications.

Medical therapy is a fundamental step in reducing the accumulation of excess fat. To reduce excess fat accumulation and excess body weight, antiobesity drugs that reduce lipid absorption in the intestine or appetite have been developed. In past years, centrally acting drugs, such as phentermine, mazindol, and fenfluramine, had been approved as antiobesity drugs, but the drugs have since been withdrawn in the USA and Europe [7, 8]. Mazindol is now available only in Japan [9]. In the 1990s, another type of antiobesity drug, orlistat, which inhibits lipid absorption in the intestine, was approved in the USA and Europe and is now also available [10]. Thereafter, sibutramine and rimonabant were developed; however, both drugs were withdrawn because of adverse effects [11]. Development of drug combinations, such as qsymia and contrave, has been recently promoted [12], and serotonin (5HT2c)-R agonist lorcaserin was accepted by the FDA in 2012 [13]. In addition, a variety of drugs with various mechanisms, such as protein tyrosine phosphatase (PTP) 1B inhibitors, microsomal triglyceride transfer protein (MTP) inhibitors, diacylglycerol acyltransferase (DGAT) 1 inhibitors, and monoacylglycerol acyltransferase (MGAT) inhibitors, have been investigated in clinical and basic stages [14–19].

Animal models have played important roles in the development of these antiobesity drugs. Obese animal models are essential to elucidate the etiology for the drug development. In the first half of this chapter, we introduce the characteristics of obese animal models. Obese animal models are divided into two types: genetic and nongenetic models. An overview of the pathophysiological features, such as body weight, blood chemical parameters, and histopathology of microangiopathy, is presented for both types. Moreover, an obese model is expected to be used as a NASH model. An overview of the development of NASH-like hepatic lesions in each model is also presented. In the second half of this chapter, results of pharmacological studies using the obese animal models for new antiobesity drugs are shown. The pharmacological effects were investigated using both genetic and nongenetic animal models.
