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

Glycolysis maintains AMPK activation in sorafenib-induced Warburg effect

Sijia Guo, Chenhao Zhang, Haiou Zeng, Yantao Xia, ... Huan Wang

Summary

Hepatocellular carcinoma (HCC) is the second deadly cancer in the world and still lacks curative treatment. Aerobic glycolysis, or Warburg effect, is a major resistance mechanism induced by first-line treatment of HCC, sorafenib, and is regulated by the master regulator of metabolism, AMPK. Activation of AMPK is required for resistance; however, activation dynamics of AMPK and its regulation is rarely studied. Engineering cells to express an AMPK activity biosensor, we monitor AMPK activation in single HCC cells in a high throughput manner during sorafenib-induced drug resistance. Sorafenib induces transient activation of AMPK, duration of which is dependent on glucose. Inhibiting glycolysis shortens AMPK activation; whereas increasing glycolysis increases its activation duration. Our data highlight that activation duration of AMPK is important for cancer evasion of therapeutic treatment and glycolysis is a key regulator of activation duration of AMPK.

Keywords

AMPK

hepatocellular carcinoma

glycolysis

drug sensitivity

sorafenib

Articles in Press

Glycolysis maintains AMPK activation in sorafenib-induced Warburg effect

Sijia Guo, Chenhao Zhang, Haiou Zeng, Yantao Xia, ... Huan Wang

Summary

Hepatocellular carcinoma (HCC) is the second deadly cancer in the world and still lacks curative treatment. Aerobic glycolysis, or Warburg effect, is a major resistance mechanism induced by first-line treatment of HCC, sorafenib, and is regulated by the master regulator of metabolism, AMPK. Activation of AMPK is required for resistance; however, activation dynamics of AMPK and its regulation is rarely studied. Engineering cells to express an AMPK activity biosensor, we monitor AMPK activation in single HCC cells in a high throughput manner during sorafenib-induced drug resistance. Sorafenib induces transient activation of AMPK, duration of which is dependent on glucose. Inhibiting glycolysis shortens AMPK activation; whereas increasing glycolysis increases its activation duration. Our data highlight that activation duration of AMPK is important for cancer evasion of therapeutic treatment and glycolysis is a key regulator of activation duration of AMPK.

Keywords

AMPK

hepatocellular carcinoma

glycolysis

drug sensitivity

sorafenib

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