Obesity is an epidemic problem in the world and is associated with several health problems, including diabetes, cardiovascular disease, respiratory failure, muscle weakness, and cancer. The precise molecular mechanisms by which obesity induces these health problems are not yet clear. To better understand the pathomechanisms of human disease, good animal models are essential. In this paper, we will analyze animal models of obesity and their use in the research of obesity-associated human health conditions and diseases such as diabetes, cancer, and obstructive sleep apnea syndrome.

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Biology of Obesity: Lessons from Animal Models of Obesity

Obesity is an increasingly important health issue in both humans and animals and has been highly correlated as a risk factor for hyperglycemic conditions in humans. Naturally occurring obesity has been extensively studied in nonhuman primates with a focus on the development of biomarkers for characterizing overweight individuals and tracking the progression of obesity to conditions such as type 2 diabetes mellitus. Animal models have provided a basic understanding of metabolism and carbohydrate physiology, and continue to contribute to ongoing research of obesity and its adverse health effects. This review focuses on spontaneous obesity in rhesus and cynomolgus macaques as a model for human obesity and type 2 diabetes mellitus, including associated risk factors for the development of obesity and obesity-related health conditions. Little is known about preventive measures to minimize obesity while maintaining a healthy colony of macaques, and numerous complexities such as social status, feeding behaviors, timing of feeding, food distribution, and stress have been identified as contributing factors to overweight body condition in both single and group housed nonhuman primates. As in humans, increased body weight and obesity in macaques affect their overall health status. These conditions may interfere with the suitability of some animals in various studies unrelated to obesity.

Obesity in rhesus and cynomolgus macaques: a comparative review of the condition and its implications for research.

The Japanese macaque (Macaca fuscata) is one species of the genus Macaca, which is now distributed in lower-latitude areas in Asia, excepting the Barbary macaque (Macaca sylvanus, which is distributed to Northwestern Africa). The genus Macaca is phylogenetically close to mangabeys and baboons (tribe Papionini; Fleagle 1999), has a medium-sized stout body, and lives either arboreally or terrestrially. According to Delson (1980), the geographical evolutionary history of Macaca is as follows: the genus arose 7–8 million years ago (MYA) in northern Africa, and the ancestor migrated to Eurasia via the Middle East around 5–6 MYA. Although the immigrants to southern Europe remained there for a long time, all of them are considered to be close to the extant Barbary macaque, that is, a conspecific or closely related species; they became extinct several 10,000 years ago. Other populations dispersed to Asia and flourished adaptationally but, because of the paucity of fossils, their exact evolutionary history has not yet been elucidated. On the basis of the supposed macaque fossil Macaca palaeoindicus (2.5–3.0 MYA) from India, the genus Macaca migrated from the Middle East to India along the seashore (southern course). However, a northern course cannot be denied because the majority of macaque fossils excavated have been from China or northern Vietnam. In particular, fossils from Yushe, Shanxi Province (ca. 5.5 MYA) suggest that a macaque ancestor migrated from Europe via Central Asia to China and then dispersed to Southeast and South Asia (Takai 2005).

Morphological Characteristics, Growth, and Aging in Japanese Macaques

Caloric restriction induces body mass loss that is often regained when restriction ends. This study aimed to determine if dietary energy density modulates the extent of post-restriction body mass regain. Water (20% wt:wt) was added to a standard dry commercially available feline diet. Twenty-seven domestic short-haired cats underwent a 20% caloric restriction on this diet. Following restriction, cats were offered the same dry diet ad libitum either without additional water or with 40% added water, therefore maintaining macronutrient composition whilst manipulating energy density. Despite no significant difference in energy intake during ad libitum consumption, post-restriction body mass regain was greater on the high energy dense (0% hydrated), compared to the low energy dense (40% hydrated) diet. The same protocol was repeated with a separate cohort of 19 cats with additional measures of physical activity, gut transit time and energy digestibility. Activity levels on the low energy dense diet were significantly higher than in cats on the high energy dense diet (p=0.030) and were similar to those recorded during caloric restriction. These results suggest that body mass gain following caloric restriction is ameliorated, and physical activity enhanced, by feeding a diet which is low in energy density due to the addition of 40% water.

https://www.abdn.ac.uk/energetics-research/publications/pdf_docs/335.pdf

The effects of increasing water content to reduce the energy density of the diet on body mass changes following caloric restriction in domestic cats.

The prevalence of obesity in the US is increasing exponentially across gender, age and ethnic groups. Obesity and a long-term hypercaloric diet result in what appears to be accelerated aging, often leading to a multi-systemic deterioration known as the metabolic syndrome. Due to their physiological similarity to humans as well as comparable rates of spontaneous obesity and diabetes mellitus, nonhuman primates provide a useful translational model for the human condition. They allow for an in vivo study of disease progression, interaction of comorbidities, and novel interventions. However, defining obesity in aged humans and nonhuman primates is difficult as the physiological changes that occur with aging are not accounted for using our current systems (BMI - body mass index and BCS - body condition score). Nonetheless, nonhuman primate studies have greatly contributed to our understanding of obesity and metabolic dysfunction and should continue to play a large role in translational research. Here, methods for defining obesity and metabolic syndrome in humans and nonhuman primates are described along with the prevalence and effects of these conditions.

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Obesity and Aging in Humans and Nonhuman Primates: A Mini-Review.

Background Japanese monkey, Macaca fuscata, is recognized as the monkey species inhabiting the northernmost area in the world, and thus likely to possess unique fat-depositing mechanisms to resist cold weather in winter. We report that obese females are present in the Wakasa group of Japanese monkey reared in an open enclosure of the Primate Research Institute, Kyoto University.



Methods and Results  Eight of 12 females were categorized as obese, showing percentage body fat of over 22%. The levels of serum leptin (mean ± SD, 4.9 ± 2.3 ng/ml) measured in these obese monkeys were significantly higher than those of non-obese peers of the same group (n = 4; 1.2 ± 0.5 ng/ml) and another Japanese monkey group (Takahama, n = 14; 0.8 ± 0.25 ng/ml); however, serum levels of adiponectin, insulin, glucose, hemoglobin A1c, and fructosamine did not differ between obese and non-obese monkeys. Few serum lipid parameters such as triglyceride and cholesterol showed lower levels in obese monkeys than their non-obese peers.



Conclusions  These results show that these obese monkeys in the Wakasa group have not developed obesity-related diseases/disorders such as diabetes. In the Wakasa group, the frequency of obese individuals was high in some maternal lineages, suggesting that genetic factors responsible for obesity may have been inherited in these lineages.

Masamitsu Abe

Papers

Characterization of obesity in Japanese monkeys (Macaca fuscata) in a pedigreed colony.