The Synergism in Hormonal and Cellular Changes in Male Mice on Long Term High Fat Exposure.

OBJECTIVE: To determine the hormonal changes that occur as a result of the long-term intake of a very-high-fat diet (VHFD) that leads to simultaneous changes in the islets of Langerhans and adipocyte cell size.

METHODS: Male mice were fed with a normal chow diet (ND, n = 15) and a VHFD (n = 30) for 2, 12, and 24 weeks. Body weight, food intake, caloric intake (fat [saturated and unsaturated], protein, and carbohydrate), hormone levels (leptin and insulin), and islet of Langerhans/adipocyte size were quantitatively recorded.

RESULTS: In VHFD-fed animals, body weight showed a significant percent increase within the first 12 weeks and then plateaued with time. VHFD-fed animals consumed significantly less food than ND at all time periods, indicating that it was the quality of food and not the quantity that caused this increase in body weight. Male mice on VHFD showed a significant increase in leptin and insulin levels, along with accompanying growth in islet and adipocyte size within the first 12 weeks, which plateaued as the mice aged. The increases in the islet and adipocyte size in VHFD-fed animals were similar to the analogous increases in hormonal levels (2 vs. 12 vs. 24 weeks). These results, therefore, suggest that in diet-induced obesity changes, shifts in hormonal levels works hand-in-hand with metabolic adjustments at the cellular level to combat the effect of fat.

CONCLUSION: Thus, mechanisms like hormonal resistance, changes in adiposity, islet size, and caloric intake with prolonged exposure to high fat are probably defensive mechanisms employed to protect against diabetes. In order to understand these complicated and nuanced effects of high fat and to comprehend the underlying mechanism associated with it, it is important to focus on long-term studies that emphasize the synergy between cellular and hormonal changes, in addition to an analysis of individual components.