IUBMB Life, 48: 109± 113, 1999 Copyright c ° 1999 IUBMB 1521-6543 / 99 $12.00 + .00 Original Research Article Effects of Genetic and Diet-Induced Obesity on Lipid Metabolism Roksan Libinaki, Mark Heffernan, Woei-Jia Jiang, Esra Ogru, Vera Ignjatovic, Robert Gianello, Lisa Trickey, Michelle Taylor, and Frank Ng Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3168, Australia Summary C57BL/ 6J obese (ob/ ob) and lean mice fed ad libitum on a nor- mal mouse chow diet (Normal), were compared with lean mice of the same age and strain fed ad libitum on a high-fat diet, consisting of the Normal diet with the addition of beef lard (Lard), from age 3 months for 34 days. The lard-fed mice were seen to have signif- icantly higher (P < 0.05) body weight in this 34-day period than that of the other two groups fed on the Normal diet. Epididymal fat depot and adipocyte cell size were signi®cantly larger (P < 0.05) in the Lard-fed lean mice and in the obese (ob/ ob) mice than were those of the Normal-fed lean mice. Dietary Lard intake did not signi®cantly affect concentrations of plasma triglyceride although those of plasma cholesterol were signi®cantly increased (P < 0.05). The development of obesity in these Lard-fed mice appeared to be accelerated and signi®cant. IUBMB Life, 48: 109± 113, 1999 Keywords Diet-induced obesity; genetic obesity; high-saturated fat diet; mice. INTRODUCTION Excess fat mass, characterising obesity, usually results from excessive energy storage over a prolonged period of time. This energy imbalance can theoretically result from excessive en- ergy intake and lower energy expenditure, such as abnormal metabolic processes, impaired thermoregulation, or reduced physical activity. The development of obesity is believed to be in¯uenced by a number of factors, including genes and envi- ronment. Studies in animal models have clearly demonstrated that these 2 distinct types of obesity exist and that their mecha- nisms of excess fat mass accumulation may differ substantially (1). First is genetic obesity, as seen in rodent strains such as the Zucker fatty (fa/ fa) rat and the obese (ob/ ob) mouse used in this Received 20 October 1998; accepted 26 January 1999. Address correspondence to Associate Professor Frank Ng. study; these animals become obese under a wide range of exper- imental conditions. If food is provided ad libitum, hyperphagia will usually occur and account for most of the excess body fat gain. If food is restricted, a decrease in energy expenditure (pri- marily thermoregulation) is seen, and the resulting positive en- ergy balance will again permit substantial body weight (2). The second basic type of obesity results from environmental inter- actions, but evidence to provide a de®nitive mechanism for this type of obesity is yet to be de®ned. With few exceptions, obesity can be induced by high-fat diets in several animal species, in- cluding monkeys, dogs, pigs, hamsters, squirrels, rats, and mice (1). Thesecafeteria-fed animals in previous studies have demon- strated increased body weight and metabolic changes that favour an increase of fat accumulation. Dietary fat is poorly regulated; that is, exc essive intake of fat at one meal is not followed by de- creased intake at the next meal (3). Fat in the diet increases the palatability of food, as well as having a higher energy density than carbohydrates and proteins. The amount of ATP produced by a given weight of fat far exceeds that produced by the same weight of carbohydrates and proteins. Support for the notion that genetic abnormalities may also contribute to obesity came with the identi®cation in 1994 of the obese gene (ob) and its protein product, leptin. Leptin is pro- duced in adipose tissue and is proposed to act as an afferent satiety signal in a feedback loop that putatively affects the ap- petite and satiety centers in the brain (4). In ob/ ob mice, which are markedly obese, the ob gene is mutated and no leptin is pro- duced; when these mice were given leptin, their food intake was reduced. The operation of the genetic factor in human obesity, however, is far more complicated. A resistance to leptin action, but not any lack of production, is believed to be the problem, and multiple genes responsible for obesity are also proposed (4). However, the ob/ ob mice provide a convenient experimen- tal model for investigations of genetic obesity. Changes in lipid synthesis and metabolism have been re- ported among diet-induced obese and genetically obese rats (5). The studies reported here were conducted to examine the 109