Cover Story Current Issue

Chronic intake of high-energy diets alters the physiological response to food and favors overconsumption. Feeding, especially of palatable food, leads to dopamine (DA) release in the Nucleus Accumbens (NAc, in the ventral striatum), prefrontal cortex (PFC) and dorsal striatum. The mesocortical (ventral tegmental area (VTA) projecting to NAc) DA system has been implicated in motivational drive and food seeking while the nigrostriatal DA (projections from the substantia nigra (SN) to the dorsal striatum) pathway plays a role in both food anticipatory behavior and reinforcement. In humans, hypersensitivity to food-associated reward may predispose to weight gain, however as obesity progresses deficit in reward signaling emerges. Individuals with obesity have reduced DRD2 availability in prefrontal brain regions compared to lean counterparts. 

Jiyoung S. Kim, Kevin C. Williams, Rebecca A. Kirkland, Ruth Schade, ... Claire B. de La Serre

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Current Issue

Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis

Yang Liu, Yue Qu, Chloe Cheng, Pei-Yin Tsai, ... Joeva J. Barrow

Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis

Objective

The activation of non-shivering thermogenesis (NST) has strong potential to combat obesity and metabolic disease. The activation of NST however is extremely temporal and the mechanisms surrounding how the benefits of NST are sustained once fully activated, remain unexplored. The objective of this study is to investigate the role of 4-Nitrophenylphosphatase Domain and Non-Neuronal SNAP25-Like 1 (Nipsnap1) in NST maintenance, which is a critical regulator identified in this study.

Methods

The expression of Nipsnap1 was profiled by immunoblotting and RT-qPCR. We generated Nipsnap1 knockout mice (N1–KO) and investigated the function of Nipsnap1 in NST maintenance and whole-body metabolism using whole body respirometry analyses. We evaluate the metabolic regulatory role of Nipsnap1 using cellular and mitochondrial respiration assay.

Results

Here, we show Nipsnap1 as a critical regulator of long-term thermogenic maintenance in brown adipose tissue (BAT). Nipsnap1 localizes to the mitochondrial matrix and increases its transcript and protein levels in response to both chronic cold and β3 adrenergic signaling. We demonstrated that these mice are unable to sustain activated energy expenditure and have significantly lower body temperature in the face of an extended cold challenge. Furthermore, when mice are exposed to the pharmacological β3 agonist CL 316, 243, the N1–KO mice exhibit significant hyperphagia and altered energy balance. Mechanistically, we demonstrate that Nipsnap1 integrates with lipid metabolism and BAT-specific ablation of Nipsnap1 leads to severe defects in beta-oxidation capacity when exposed to a cold environmental challenge.

Conclusion

Our findings identify Nipsnap1 as a potent regulator of long-term NST maintenance in BAT.

 

Articles in Press

Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis

Yang Liu, Yue Qu, Chloe Cheng, Pei-Yin Tsai, ... Joeva J. Barrow

Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis

Objective

The activation of non-shivering thermogenesis (NST) has strong potential to combat obesity and metabolic disease. The activation of NST however is extremely temporal and the mechanisms surrounding how the benefits of NST are sustained once fully activated, remain unexplored. The objective of this study is to investigate the role of 4-Nitrophenylphosphatase Domain and Non-Neuronal SNAP25-Like 1 (Nipsnap1) in NST maintenance, which is a critical regulator identified in this study.

Methods

The expression of Nipsnap1 was profiled by immunoblotting and RT-qPCR. We generated Nipsnap1 knockout mice (N1–KO) and investigated the function of Nipsnap1 in NST maintenance and whole-body metabolism using whole body respirometry analyses. We evaluate the metabolic regulatory role of Nipsnap1 using cellular and mitochondrial respiration assay.

Results

Here, we show Nipsnap1 as a critical regulator of long-term thermogenic maintenance in brown adipose tissue (BAT). Nipsnap1 localizes to the mitochondrial matrix and increases its transcript and protein levels in response to both chronic cold and β3 adrenergic signaling. We demonstrated that these mice are unable to sustain activated energy expenditure and have significantly lower body temperature in the face of an extended cold challenge. Furthermore, when mice are exposed to the pharmacological β3 agonist CL 316, 243, the N1–KO mice exhibit significant hyperphagia and altered energy balance. Mechanistically, we demonstrate that Nipsnap1 integrates with lipid metabolism and BAT-specific ablation of Nipsnap1 leads to severe defects in beta-oxidation capacity when exposed to a cold environmental challenge.

Conclusion

Our findings identify Nipsnap1 as a potent regulator of long-term NST maintenance in BAT.

 

2021 impact factor: 8.568

You are what you eat

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