AMP-activated Protein Kinase Plays a Role in the Control of Food Intake*

By U. Andersson, K. Filipsson, C. Abbott, A. Woods, Kirsty L. Smith, Stephen R. Bloom, David Carling, C. Small. Journal of Biological Chemistry, 2004

779 citations recorded by the source corpus.

AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that acts as an intracellular energy sensor maintaining the energy balance within the cell. The finding that leptin and adiponectin activate AMPK to alter metabolic pathways in muscle and liver provides direct evidence for this role in peripheral tissues. The hypothalamus is a key regulator of food intake and energy balance, coordinating body adiposity and nutritional state in response to peripheral hormones, such as leptin, peptide YY-(3–36), and ghrelin. To date the hormonal regulation of AMPK in the hypothalamus, or its potential role in the control of food intake, have not been reported. Here we demonstrate that counter-regulatory hormones involved in appetite control regulate AMPK activity and that pharmacological activation of AMPK in the hypothalamus increases food intake. In vivo administration of leptin, which leads to a reduction in food intake, decreases hypothalamic AMPK activity. By contrast, injection of ghrelin in vivo, which increases food intake, stimulates AMPK activity in the hypothalamus. Consistent with the effect of ghrelin, injection of 5-amino-4-imidazole carboxamide riboside, a pharmacological activator of AMPK, into either the third cerebral ventricle or directly into the paraventricular nucleus of the hypothalamus significantly increased food intake. These results suggest that AMPK is regulated in the hypothalamus by hormones which regulate food intake. Furthermore, direct pharmacological activation of AMPK in the hypothalamus is sufficient to increase food intake. These findings demonstrate that AMPK plays a role in the regulation of feeding and identify AMPK as a novel target for anti-obesity drugs.

Subfields: Endocrine and Autonomic Systems, Molecular Biology, Nutrition and Dietetics

View Paper: https://www.semanticscholar.org/paper/bf6d24d084099c523575e97bfbe1e8d25c9d3346

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrine and Autonomic Systems

1. D. Hardie
2. Toshimasa Yamauchi
3. B. Kahn
4. M. Oba
5. Roger Cone
6. B. Bradford
7. M. Allen
8. J. Oakhill

In Molecular Biology

1. D. Hardie
2. R. Shaw
3. G. Steinberg
4. David Carling
5. S. Hawley
6. Bruce E. Kemp
7. Fiona A. Ross
8. J. Scott

In Nutrition and Dietetics

1. D. Hardie
2. Toshimasa Yamauchi
3. B. Kahn
4. Roger Cone
5. Takashi Kadowaki
6. Haiming Cao

Citations in the corpus

• Kisspeptins and reproduction: physiological roles and regulatory mechanisms. (2012, background): “In good agreement, leptin has been shown to inhibit hypothalamic AMPK activity, whereas the orexigenic hormone ghrelin stimulates it (10).”
• AMPK and PPARd Agonists Are Exercise Mimetics (2008, positive): “In mammals, AMPK has been shown to contribute to glucose homeostasis, appetite, and exercise physiology (Andersson et al., 2004; Hardie, 2007; Kubota et al., 2007; Mu et al., 2001; Minokoshi et al., 2004; Thomson et al., 2007).”
• AMP‐activated protein kinase – development of the energy sensor concept (2006, background): “Moreover, activation of AMPK by pharmacological means, or by over-expression of activated AMPK mutants, inhibits insulin release by pancreatic β cells, while in the hypothalamus it stimulates feeding behaviour (Salt et al. 1998; da Silva Xavier et al. 2003; Andersson et al. 2004; Minokoshi et al. 20”
• AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. (2005, background): “On the other hand, orexigenic peptides such as the gutderived hormone ghrelin (Andersson et al., 2004) and the neuropeptide agouti-related peptide (Minokoshi et al.”
• The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. (2004, background): “For example, when energy availability is limited in rodents, AMPK functions to restore normal energy levels by stimulating glucose uptake in skeletal muscle and glycolysis in the heart and by promoting feeding by regulating a hypothalamic circuit (Marsin et al. 2000; Mu et al. 2001; Andersson et al.”
• AMPK in Health and Disease. (2009, background): “Since the constitutively active AMPK fragment 1 (1-312) is not activated by the PT1 compound, it is proposed that PT1 acts by reversing the autoinhibition of the AIS (313-335).”
• Adipose tissue as an endocrine organ. (2010, background): “Leptin administration also suppresses the activity of AMP-activated protein kinase (AMPK) in the paraventricular nucleus (PVN) and arcuate nucleus (ARC) of the hypothalamus (Andersson et al., 2004; Steinberg et al., 2006a; Minokoshi et al., 2004).”
• Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake. (2007, background): “It has been suggested that adiponectin is an orexigenic hormone and that it may stimulate the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), downstream of AMPK, in the hypothalamus (Hardie, 2004; Andersson et al., 2004; Carling, 2005; Xue and Kahn, 2006).”