Neuroprotective effects of leptin in the context of obesity and metabolic disorders.
As the population of the world ages, the prevalence of neurodegenerative disease continues to rise, accompanied by increases in disease burden related to obesity and metabolic disorders. Thus, it will be essential to develop tools for preventing and slowing the progression of these major disease entities. Epidemiologic studies have shown strong associations between obesity, metabolic dysfunction, and neurodegeneration, while animal models have provided insights into the complex relationships between these conditions. Experimentally, the fat-derived hormone leptin has been shown to act as a neuroprotective agent in various animal models of dementia, toxic insults, ischemia/reperfusion, and other neurodegenerative processes. Specifically, leptin minimizes neuronal damage induced by neurotoxins and pro-apoptotic conditions. Leptin has also demonstrated considerable promise in animal models of obesity and metabolic disorders via modulation of glucose homeostasis and energy intake. However, since obesity is known to induce leptin resistance, we hypothesize that resistance to the neuroprotective effects of leptin contributes to the pathogenesis of obesity-associated neurodegenerative diseases. This review aims to explore the literature pertinent to the role of leptin in the protection of neurons from the toxic effects of aging, obesity and metabolic disorders, to investigate the physiological state of leptin resistance and its causes, and to consider how leptin might be employed therapeutically in the prevention and treatment of neurodegenerative disease.
Diabetes Research Center, Albert Einstein College of Medicine, USA.
Cecilia
C
Davis
Diabetes Research Center, Albert Einstein College of Medicine, USA.
Jeremy
J
Mudd
Diabetes Research Center, Albert Einstein College of Medicine, USA.
Meredith
M
Hawkins
D000544:Alzheimer Disease / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D020738:Leptin / Q000378:metabolism* / Q000627:therapeutic use; D051379:Mice; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000627:therapeutic use; D009765:Obesity / Q000378:metabolism* / Q000517:prevention & control; D010300:Parkinson Disease / Q000378:metabolism* / Q000517:prevention & control; D051381:Rats
D020738:Leptin; D018696:Neuroprotective Agents
Diabetes; Leptin; Leptin resistance; Metabolic disorder; Neurodegeneration; Obesity