Abstract
Cocaine- and amphetamine-regulated transcript (CART) is widely expressed in the hypothalamus and an important regulator of energy homeostasis; however, the specific contributions of different CART neuronal populations to this process are not known. Here, we show that depolarization of mouse arcuate nucleus (Arc) CART neurons via DREADD technology decreases energy expenditure and physical activity, while it exerts the opposite effects in CART neurons in the lateral hypothalamus (LHA). Importantly, when stimulating these neuronal populations in the absence of CART, the effects were attenuated. In contrast, while activation of CART neurons in the LHA stimulated feeding in the presence of CART, endogenous CART inhibited food intake in response to Arc CART neuron activation. Taken together, these results demonstrate anorexigenic but anabolic effects of CART upon Arc neuron activation, and orexigenic but catabolic effects upon LHA-neuron activation, highlighting the complex and nuclei-specific functions of CART in controlling feeding and energy homeostasis.
Highlights
The neuropeptide cocaine- and amphetamine-regulated transcript (CART) is encoded by Cart prepropeptide (Cartpt) and involved in the regulation of a diverse range of physiological functions including food intake and energy homeostasis, thermoregulation, reward as well as stress processing (Lau and Herzog, 2014; Subhedar et al, 2014)
The present study demonstrates the critical and distinct roles of CART neurons in the arcuate nucleus (Arc) and lateral hypothalamic area (LHA) in the control of feeding behavior and energy homeostasis, and more importantly represents the first report to dissect the specific contribution of CART to these processes
Activation of Arc CART neurons leads to significant decreases in energy expenditure, locomotion and body temperature, and these effects are solely due to the contribution of CART since they are absent in ArcfihM3Dq Cartptcre/cre mice that are devoid of endogenous CART
Summary
The neuropeptide cocaine- and amphetamine-regulated transcript (CART) is encoded by Cart prepropeptide (Cartpt) and involved in the regulation of a diverse range of physiological functions including food intake and energy homeostasis, thermoregulation, reward as well as stress processing (Lau and Herzog, 2014; Subhedar et al, 2014). The administration of CART into specific hypothalamic nuclei demonstrated orexigenic effects (Abbott et al, 2001), indicating location-dependent functions of CART. In the hypothalamus, both the arcuate nucleus (Arc) and the lateral hypothalamic area (LHA) show high expression of CART and play a central role in a variety of homeostatic functions, including the regulation of energy homeostasis (Lau and Herzog, 2014). Two populations of neurons located in the Arc are regarded as the main regulators of energy homeostasis, the orexigenic neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons and the anorexigenic proopiomelanocortin (POMC) neurons, which to some extent coexpress CART
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