Control of metabolism by nutrient-regulated nuclear receptors acting in the brain.
Today, we are witnessing a rising incidence of obesity worldwide. This increase is due to a sedentary life style, an increased caloric intake and a decrease in physical activity. Obesity contributes to the appearance of type 2 diabetes, dyslipidemia and cardiovascular complications due to atherosclerosis, and nephropathy. Therefore, the development of new therapeutic strategies may become a necessity. Given the metabolism controlling properties of nuclear receptors in peripheral organs (such as liver, adipose tissues, pancreas) and their implication in various processes underlying metabolic diseases, they constitute interesting therapeutic targets for obesity, dyslipidemia, cardiovascular disease and type 2 diabetes. The recent identification of the central nervous system as a player in the control of peripheral metabolism opens new avenues to our understanding of the pathophysiology of obesity and type 2 diabetes and potential novel ways to treat these diseases. While the metabolic functions of nuclear receptors in peripheral organs have been extensively investigated, little is known about their functions in the brain, in particular with respect to brain control of energy homeostasis. This review provides an overview of the relationships between nuclear receptors in the brain, mainly at the hypothalamic level, and the central regulation of energy homeostasis. In this context, we will particularly focus on the role of PPARα, PPARγ, LXR and Rev-erbα.
Univ Lille Nord de France, INSERM UMR1011, UDSL, Institut Pasteur de Lille, Lille, France.
Kadiombo
K
Bantubungi
Janne
J
Prawitt
Bart
B
Staels
D050154:Adiposity / Q000502:physiology*; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D050171:Dyslipidemias / Q000378:metabolism; D002149:Energy Intake / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D000071518:Liver X Receptors; D051379:Mice; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats
D000071518:Liver X Receptors; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha; D047495:PPAR gamma