From Obesity to Hippocampal Neurodegeneration: Pathogenesis and Non-Pharmacological Interventions

High-caloric diet and physical inactivity predispose individuals to obesity and diabetes, which are risk factors of hippocampal neurodegeneration and cognitive deficits. Along with the adipose-hippocampus crosstalk, chronically inflamed adipose tissue secretes inflammatory cytokine could trigger neuroinflammatory responses in the hippocampus, and in turn, impairs hippocampal neuroplasticity under obese and diabetic conditions. Hence, caloric restriction and physical exercise are critical non-pharmacological interventions to halt the pathogenesis from obesity to hippocampal neurodegeneration. In response to physical exercise, peripheral organs, including the adipose tissue, skeletal muscles, and liver, can secret numerous exerkines, which bring beneficial effects to metabolic and brain health. In this review, we summarized how chronic inflammation in adipose tissue could trigger neuroinflammation and hippocampal impairment, which potentially contribute to cognitive deficits in obese and diabetic conditions. We also discussed the potential mechanisms underlying the neurotrophic and neuroprotective effects of caloric restriction and physical exercise by counteracting neuroinflammation, plasticity deficits, and cognitive impairments. This review provides timely insights into how chronic metabolic disorders, like obesity, could impair brain health and cognitive functions in later life.

Automated summary

A high-caloric diet and lack of physical activity can lead to obesity and diabetes, increasing the risk of hippocampal neurodegeneration and cognitive deficits. Caloric restriction and physical exercise are crucial non-pharmacological interventions to prevent the development of hippocampal neurodegeneration in obese and diabetic individuals, while exercise-induced exerkines from peripheral organs have beneficial effects on brain health. This review highlights how chronic inflammation in adipose tissue may contribute to neuroinflammation and hippocampal impairment, potentially leading to cognitive deficits in obese and diabetic conditions.