**1. Introduction**

The rapid increase in the rate of obesity is a health problem critical in developed countries. Obesity is associated with a number of health problems that are often summarized together as metabolic syndrome and involve the development of insulin resistance, type 2 diabetes, cardiovascular disease and fatty liver disease [1].

Nonalcoholic Fatty Liver Disease (NAFLD) is the leading cause of chronic liver disease affecting 20–30% of the world's adult population, and is characterized by a buildup of fat, mainly in the form of triglycerides, in the hepatocyte cytoplasm, exceeding 5–10% of the cell weight, verified histologically or by imaging techniques. It requires exclusion of other causes of steatosis, such as excessive alcohol consumption, drugs or genetic diseases [2, 3]. About 20–30% of individuals with NAFLD can develop Non-alcoholic steatohepatitis (NASH) [4], a more severe disease condition related to metabolic abnormalities associated with obesity, namely hyperinsulinemia, dyslipidemia, and ectopic lipid accumulation [5]. More specifically, NASH is associated with lobular inflammation, hepatocellular damage and/or hepatic fibrosis [4].

NAFLD is common in Western countries, usually associated with the main characteristics of the metabolic syndrome, such as obesity, insulin resistance and hyperlipidemia [6]. Data from the U.S. National Health and Nutrition Examination Surveys, collected from 1988 to 2008, show a 2-fold higher prevalence of NAFLD, concomitant with the increased or increasing prevalence of metabolic conditions such as obesity and insulin resistance [7].

In this context, obesity induction with the development of hepatic steatosis in animal models is discussed. Animal models of obesity focused on NAFLD and NASH, as well as pathophysiological aspects related to obesity and liver diseases were systematically addressed in this chapter.

albumin. The peripheral tissues, in turn, receive fatty acids as substrates for oxidation (mainly muscle) and storage (adipose tissue), through the action of endothelial lipoprotein lipase on particles rich in circulating triglycerides, either VLDL secreted by the liver, or chylomicrons

**Figure 1.** NAFLD mechanisms. Associated factors such as increased lipolysis and de novo hepatic lipogenesis (DNL), decreased free fatty acid oxidation and hepatic secretion of low density lipoprotein (VLDL) aggravate the onset of the disease. The action of Mitochondrial β-oxidation contributes to the synthesis of adenosine triphosphate (ATP), however

Animal Models of Obesity Characterized by Non-alcoholic Fatty Liver Disease (NAFLD)

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During fat digestion, medium and short chain fatty acids are absorbed directly into the portal circulation. Whereas long chain fatty acids (C > 14) are mainly reesterified in chylomicrons, but a proportion of long chain unsaturated free fatty acids (FFA) enters the portal

According to the hypothesis on hepatic lipotoxic lesions, certain FFAs and their metabolites flow through the liver and cause NAFLD/NASH. Dietary intake plays an important role in the generation of FFA. Excess carbohydrate consumption, particularly fructose, leads to *de novo* lipogenesis. Excess calories and fats can result in accumulation of lipids in adipose tissue, and finally, the stored fatty acids are released through lipolysis. Free fatty acids generated by lipogenesis, lipolysis or other mechanisms have three potential destinations: triglycerides

Hepatic mitochondria play an important role in the oxidation of fatty acids and in the synthesis of ATP. Mitochondrial β-oxidation is a pathway for the elimination of fatty acids, but results in the generation of reactive oxygen species (ROS). In most circumstances, the endogenous antioxidant mechanisms are able to protect against cellular damage caused by ROS. However, in the configuration of impaired mitochondrial function related to obesity

delivered to lymphatic circulation after intestinal absorption of lipids [10].

formation, oxidation and elimination, or intermediate lipid formation [11].

circulation [10].

results in the increase of reactive oxygen species.
