page_title: Diet-induced obesity model
section_title: Experimental
hierarchical_section_title: Diet-induced obesity model / Limitations / Experimental
caption_attribution_description: English: The limitations that exist when performing a diet induced obesity model on different animals.
context_page_description: The diet-induced obesity model is an animal model used to study obesity using animals that have obesity caused by being fed high-fat or high-density diets. It is intended to mimic the most common cause of obesity in humans. Typically mice, rats, dogs, or non-human primates are used in these models. These animals can then be used to study in vivo obesity, obesity's comorbidities, and other related diseases. Users of such models must take into account the duration and type of diet as well as the environmental conditions and age of the animals, as each may promote different bodyweights, fat percentages, or behaviors.
  Driven by the worldwide epidemic of obesity, particularly in the Western world, the DIO model has been integral in understanding the relationship between high-fat/high-density diets and obesity, including the discovery of Akt and mTOR, signals in the body linked to obesity and insulin resistance. However, while many insights into the control of obesity have come from experiments since its introduction in 1949, the use of animal models does restrict our ability to extrapolate findings to humans.
context_section_description: Intra and Inter Laboratories results can differ due to variation in the experimental factors such as the protocol used, housing, temperature, light/dark cycle and the duration of study.
  Laboratories temperature which are usually (18-22 °C) are lower than the thermoneutrality of model organisms like mice which are about 30 °C. That can introduce hyperphagia in the organism in effort of increasing their metabolism to generate heat energy for the body. This level of thermal stress can also have unaccounted effects on the organism's other metabolic processes.
  Furthermore, the spatial confinements in housing organisms can affect the brain chemistry in social creatures like mice and rats, making them more vulnerable to slower brain development and abnormalities due to the lack of social interactions. The psychological effects can introduce further discrepancy in the studies that makes it difficult to render proper data and further hinders the possibility of recapitulating such experiments in humans.
  Rodents are nocturnal and are mostly feeding at night, in their natural habitat. The changes in the light/dark cycle of laboratories can alter their circadian rhythm which can affect their metabolism. Besides that several studies usedgenetically modified mouse models that have decreased circadian rhythmicity gene. These cases have resulted in the increase of metabolic syndrome in the mouse models as well as resulted in obesity. The change in the phenotype can be a result of genetic modification of circadian clock gene, high fat diet, disruption of the circadian cycle by changes in light and dark cycle, or a combination of all the factors. Further research is required to find the exact cause.
  The cause of type 2 diabetes mellitus in humans are far more complicated than the sole consumption of a high fat diet. The mental, emotional and cultural factors along with insulin resistance and hyperphagia are known to increase the occurrence of type 2 diabetes in humans. However, type 2 diabetes in model organisms are introduced via surgery of partial or whole pancreas, or using chemicals such as streptozotocin. Streptozotocin inhibits the ability of pancreatic β cells to produce insulin, and depending on the dosage used, the result can be partial or absolute inhibition. It can also interfere with other cell signalling pathways as well as affects the content of certain isozymes in organs like liver, brain and kidneys. The lack of proper representation of the undertaking of the experiment can introduce type 2 diabetes, but fails to reflect the mechanism through which these disease takes place in humans.
caption: The limitations that exist when performing a diet induced obesity model on different animals. Adapted from Tanja Y. Reuter Table 1.[3]  Nematode Information.[31]  Primate Information.[32]
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