Title |
Impaired Striatal Akt Signaling Disrupts Dopamine Homeostasis and Increases Feeding
|
---|---|
Published in |
PLOS ONE, September 2011
|
DOI | 10.1371/journal.pone.0025169 |
Pubmed ID | |
Authors |
Nicole Speed, Christine Saunders, Adeola R. Davis, W. Anthony Owens, Heinrich J. G. Matthies, Sanaz Saadat, Jack P. Kennedy, Roxanne A. Vaughan, Rachael L. Neve, Craig W. Lindsley, Scott J. Russo, Lynette C. Daws, Kevin D. Niswender1, Aurelio Galli |
Abstract |
The prevalence of obesity has increased dramatically worldwide. The obesity epidemic begs for novel concepts and therapeutic targets that cohesively address "food-abuse" disorders. We demonstrate a molecular link between impairment of a central kinase (Akt) involved in insulin signaling induced by exposure to a high-fat (HF) diet and dysregulation of higher order circuitry involved in feeding. Dopamine (DA) rich brain structures, such as striatum, provide motivation stimuli for feeding. In these central circuitries, DA dysfunction is posited to contribute to obesity pathogenesis. We identified a mechanistic link between metabolic dysregulation and the maladaptive behaviors that potentiate weight gain. Insulin, a hormone in the periphery, also acts centrally to regulate both homeostatic and reward-based HF feeding. It regulates DA homeostasis, in part, by controlling a key element in DA clearance, the DA transporter (DAT). Upon HF feeding, nigro-striatal neurons rapidly develop insulin signaling deficiencies, causing increased HF calorie intake. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 1 | 50% |
Members of the public | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | <1% |
Unknown | 112 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 34 | 30% |
Researcher | 12 | 11% |
Student > Master | 12 | 11% |
Student > Doctoral Student | 9 | 8% |
Student > Bachelor | 8 | 7% |
Other | 19 | 17% |
Unknown | 19 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 27 | 24% |
Neuroscience | 20 | 18% |
Medicine and Dentistry | 19 | 17% |
Biochemistry, Genetics and Molecular Biology | 7 | 6% |
Psychology | 7 | 6% |
Other | 15 | 13% |
Unknown | 18 | 16% |