Molecular physiology of weight regulation in mice and humans.

Division of Molecular Genetics and Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
International journal of obesity (2005) (Impact Factor: 5.39). 01/2009; 32 Suppl 7:S98-108. DOI: 10.1038/ijo.2008.245
Source: PubMed

ABSTRACT Evolutionary considerations relating to efficiency in reproduction, and survival in hostile environments, suggest that body energy stores are sensed and actively regulated, with stronger physiological and behavioral responses to loss than gain of stored energy. Many physiological studies support this inference, and suggest that a critical axis runs between body fat and the hypothalamus. The molecular cloning of leptin and its receptor-projects based explicitly on the search for elements in this axis-confirmed the existence of this axis and provided important tools with which to understand its molecular physiology. Demonstration of the importance of this soma-brain reciprocal connection in body weight regulation in humans has been pursued using both classical genetic approaches and studies of physiological responses to experimental weight perturbation. This paper reviews the history of the rationale and methodology of the cloning of leptin (Lep) and the leptin receptor (Lepr), and describes some of the clinical investigation characterizing this axis.

1 Follower
  • Source
    Nutrition 01/2014; 31(1). DOI:10.1016/j.nut.2014.10.002 · 3.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Alzheimer's disease (AD) is a complex neurodegenerative disorder, which involves many underlying pathological processes. Recently, it has been demonstrated that AD also includes impairments of insulin signaling in the brain. Type 2 diabetes is a risk factor for AD, and AD and diabetes share a number of pathologies. The classical hallmarks of AD are senile plaques and neurofibrillary tangles, which consist of amyloid-β and hyperphosphorylated tau. Based on the two hallmarks, transgenic animal models of AD have been developed, which express mutant human genes of amyloid precursor protein, presenilin-1/2, and tau. It is likely that these mouse models are too limited in their pathology. In this work, we describe mouse models that model diabetes and show insulin signaling impairment as well as neurodegenerative pathologies that are similar to those seen in the brains of AD patients. The combination of traditional AD mouse models with induced insulin impairments in the brain may be a more complete model of AD. Interestingly, AD mouse models treated with drugs that have been developed to cure type 2 diabetes have shown impressive outcomes. Based on these findings, several ongoing clinical trials are testing long lasting insulin analogues or GLP-1 mimetics in patients with AD.
    Reviews in the neurosciences 12/2013; 24(6):607-615. DOI:10.1515/revneuro-2013-0034 · 3.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Restricted food intake is associated with increased physical activity, very likely an evolutionary advantage, initially both functional and rewarding. The hyperactivity of patients with anorexia nervosa, however, is a main problem for recovery. This seemingly paradoxical reward of hyperactivity in anorexia nervosa is one of the main aspects in our framework for the neurobiological changes that may underlie the development of the disorder. Here, we focus on the neurobiological basis of hyperactivity and reward in both animals and humans suggesting that the mesolimbic dopamine and hypothalamic orexin neurons play central roles. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.
    Physiology & Behavior 03/2010; 100(5):490-5. DOI:10.1016/j.physbeh.2010.03.016 · 3.03 Impact Factor


Available from