Abstract
Lipoprotein lipase (LPL) is expressed in different areas of the brain, including the hypothalamus and plays an important role in neural control of the energy balance, including feeding behavior and metabolic fluxes. This study tested the hypothesis that hypothalamic LPL participates in the control of body temperature. We first showed that cold exposure induces decreased activity and expression of LPL in the mouse hypothalamus. We then selectively deleted LPL in the mediobasal hypothalamus (MBH) through an adeno-associated virus approach in LPL-floxed mice and generated MBHΔLpl mice with 30–35% decrease in hypothalamic LPL activity. Results showed a decrease in body temperature in MBHΔLpl mice when compared with controls at 22°C. Exposure to cold (4°C for 4 h) decreased the body temperature of the control mice while that of the MBHΔLpl mice remained similar to that observed at 22°C. MBHΔLpl mice also showed increased energy expenditure during cold exposure, when compared to controls. Finally, the selective MBH deletion of LPL also increased the expression of the thermogenic PRMD16 and Dio2 in subcutaneous and perigonadal adipose tissues. Thus, the MBH LPL deletion seems to favor thermogenesis. These data demonstrate that for the first time hypothalamic LPL appears to function as a regulator of body temperature and cold-induced thermogenesis.
Highlights
Adaptation to change in ambient temperature, especially cold exposure, is one of the mechanisms essential to the survival of mammals
We first demonstrated that hypothalamic Lipoprotein lipase (LPL) mRNA expression and activity were regulated as a function of ambient temperatures between 22 and 4oC
Cold exposure induced a selective decrease in both LPL activity and gene expression in hypothalamus with no change in mRNA expression in the hippocampus, striatum, or cerebral cortex when temperature dropped from 22 to 4°C
Summary
Adaptation to change in ambient temperature, especially cold exposure, is one of the mechanisms essential to the survival of mammals. This adaptation involves numerous signals of neural or hormonal origin and acute responses or acclimatization to prolonged cold exposures [1]. The hypothalamus is a key area of central nervous system (CNS) involved in the adaptation to cold exposure. Afferent signals from the skin are sensed by the preoptic area of the anterior hypothalamus. The measurement of c-fos expression suggests a role for the dorsomedial, medial, and the ventromedial hypothalamus after cold exposure in rats [2].
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