Abstract
Scope: The hypothalamus is a key brain region involved in the control of feeding and energy expenditure. Hypothalamic inflammation and oxidative stress are landmarks of both obesity and aging processes, although the molecular mechanisms are still unknown. Therefore, with the aim to understand the neurobiological mechanisms of energy homeostasis during aging, we evaluate the effects of long feeding high-fat diet (HFD) in rats, at different age, on modulation of hypothalamic molecular pathway, oxidative stress, and inflammation.Procedures: Male Wistar rats were divided into two groups: control group, receiving standard diet (CD), and treated group, receiving HFD. Both groups were treated with the appropriate diet for 1, 3, 6, 12, or 18 weeks. We investigated energy balance and body composition, as well as lipid profile, homeostatic model assessment index, and inflammatory state in serum. Furthermore, we also analyzed, at hypothalamic level, inflammation and oxidative stress, and adenosine monophosphate-dependent kinase (AMPK) and pAMPK expression levels.Results: Our data showed that aging and HFD induce increased energy intake and energy efficiency and decreased energy expenditure associated, at hypothalamic level, with inflammation and oxidative stress and activation of AMPK.Conclusion: Our results indicate that the age at which HFD feeding starts and the diet duration are critical in obesity development. The prolonged activation of hypothalamic AMPK may be related to the alterations in energy homeostasis.
Highlights
The prevalence of obesity is progressively increasing worldwide and is reaching epidemic proportions
Since the molecular mechanisms linking the high-fat diet (HFD) administration to the inflammatory response at hypothalamic level is not completely known, we studied the effect of long-term high-fat feeding on the activation of adenosine monophosphate-dependent kinase (AMPK) in the hypothalamus
These results suggest that the increase in energy intake observed in HFD animals may depend on the activation of the hypothalamic AMPK pathway
Summary
The prevalence of obesity is progressively increasing worldwide and is reaching epidemic proportions This alarming increase is mainly related to sedentary lifestyle and high consumption of fat-rich food. It has been demonstrated that both the consumption of a high-fat diet (HFD) and the aging process evoke an inflammatory response in the hypothalamus, inducing resistance to insulin and leptin. These hypothalamic malfunctions result in a defective control of food intake and energy expenditure, leading to hyperphagia, obesity, and type 2 diabetes (Cavadas et al, 2016). Hypothalamic inflammation has been identified as a crucial step in the development of obesity and in the aging processes, the molecular mechanisms underlying the inflammatory response of hypothalamic neurons to obesity and aging is still partially unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
