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Minnesota Obesity Center

2006 Grant Award - Kevin WIckman, Ph.D.

GIRK$: A New Obesity Gene?

Kevin Wickman, Ph.D.
Department of Pharmacology, University of Minnesota

Obesity is a global epidemic.  The underlying premise of this proposal is that the identification of new genetic factors predisposing individuals to unhealthy weight gain may improve risk assessments and reveal novel targets for pharmacological interventions designed to treat obesity.

The goal of the proposed research is to gain a detailed understanding of an adult-onset overweight phenotype manifested in mice lacking one subunit (GIRK4) of a potassium ion channel activated in a G protein-dependent manner by neurotransmitters and hormones such as somatostatin, serotonin, dopamine, y-aminobutyric acid (GABA), and opioids. The tissue distribution of GIRK4 is limited, and thus its conspicuous presence in glucagon-secreting pancreatic a-cells and in feeding-relevant neurons of the ventromedial hypothalamic nucleus suggests likely anatomical loci underlying the adult-onset weight gain phenotype.

A multi-disciplinary effort is proposed that will yield a rigorous characterization of this interesting phenotype while exploring roles for GIRK4 in novel aspects of energy intake and expenditure.

Experiments are proposed to:

  1. Characterize the adult-onset weight gain seen in GIRK4 knockout mice,
  2. Probe the contribution of GIRK channels to the inhibitory effects of feeding-relevant neurotransmitters on ventromedial hypothalamic neurons, and
  3. Determine whether GIRK channels mediate the inhibitory effect of somatostatin on mouse pancreatic islet a-cells.

With these studies, molecular and cellular details of novel signaling pathways influencing energy intake and expenditure will emerge, as will a clearer picture of how dysfunction in such pathways can translate into unhealthy weight gain.

2006 Awards:

ZEB1 and the Development of Obesity

Oxyntomodulin and the Regulation of Non-Exercise Activity Thermogenesis

Hypothalamic Acyl-CoA Metabolism and Food Intake Regulation

Parents as the Agent of Change for Childhood Obesity

Identifying Novel Roles of Lipocalin 2 in Insulin Action and Glucose Metabolism

GIRK$: A New Obesity Gene?

Recipients of:

2010 Grant Awards
2008 Grant Awards
2006 Grant Awards
2004 Grant Awards
2003 Grant Awards
2002 Grant Awards
2001 Grant Awards
2000 Grant Awards
1999 Grant Awards
1998 Grant Awards
1997 Grant Awards
1996 Grant Awards
1995 Grant Awards