Obese inducing brain mechanism

September 15, 2017, National Institutes of Natural Sciences
Weekly body weights by wild-type (WT) and Ptprj-KO (KO) male mice fed a high fat/high sucrose diet (HF/HSD) from 4 of age (left). Daily ND intake by WT and KO mice during 12 weeks of age on HF/HSD (right). Credit: NIBB

Leptin is an adipocyte-derived hormone that stimulates hypothalamic neurons to strongly inhibit food intake. Leptin signaling in the hypothalamus, a part of the mid-brain, thus plays a crucial role in the regulation of body weight: Leptin resistance, in which leptin signaling is disrupted, is a major obstacle to the improvement of obesity. However, the exact mechanisms underlying leptin resistance in obese patients have yet to be determined.

The research group of Professor Masaharu Noda, Associate Professor Takafumi Shintani, and a graduate student Satoru Higashi of the National Institute for Basic Biology (NIBB) demonstrated that phosphatase receptor type J (PTPRJ) inhibits leptin signaling and that induction of PTPRJ in the hypothalamus is a cause of leptin resistance.

They showed that Ptprj is expressed in together with leptin receptors, and that PTPRJ inhibits activation of the through dephosphorylation of JAK2, a associated with the leptin receptor.

Ptprj-deficient (Ptprj-KO) mice showed no growth retardation, but exhibited lower weight gain due to lower food intake and a lower adiposity, than wild-type (WT) mice. Importantly, PTPRJ expression in the hypothalamus was up-regulated by diet-induced obesity, and, thus, diet-induced leptin resistance did not occur in Ptprj-KO mice.

Yellow and blue regions indicate fat and lean tissue, respectively. Credit: NIBB

Furthermore, the overexpression of PTPRJ in the hypothalamus induced leptin resistance in lean mice. These results strongly indicate that PTPRJ plays critical roles in the development of leptin resistance. The inhibition of PTPRJ may be a potential strategy for improving obesity.

Leptin (500 ng) or vehicle was i.c.v. injected as indicated 1 h before the onset of the dark phase in WT and KO mice. Credit: NIBB

Explore further: Voluntary exercise by animals prevents weight gain, despite high-fat diet

More information: Takafumi Shintani et al, PTPRJ Inhibits Leptin Signaling, and Induction of PTPRJ in the Hypothalamus Is a Cause of the Development of Leptin Resistance, Scientific Reports (2017). DOI: 10.1038/s41598-017-12070-7

Related Stories

Voluntary exercise by animals prevents weight gain, despite high-fat diet

May 18, 2011
(Medical Xpress) -- University of Cincinnati (UC) researchers have found that animals on a high-fat diet can avoid weight gain if they exercise.

Obesity research finds leptin hormone isn't the overeating culprit

May 15, 2015
For years, scientists have pointed to leptin resistance as a possible cause of obesity. Research led by investigators at the University of Cincinnati (UC) Metabolic Diseases Institute, however, found that leptin action isn't ...

Manipulating a type of brain cell gets weight loss results in mice

July 28, 2017
A new study has found something remarkable: the activation of a particular type of immune cell in the brain can, on its own, lead to obesity in mice. This striking result provides the strongest demonstration yet that brain ...

Target for obesity drugs comes into focus

October 11, 2012
(Medical Xpress)—Researchers at the University of Michigan have determined how the hormone leptin, an important regulator of metabolism and body weight, interacts with a key receptor in the brain.

Rap1, a potential new target to treat obesity

October 21, 2016
Scientists at Baylor College of Medicine, the National Institutes of Health and Virginia Tech Carilion Research Institute have discovered a new mechanism in the mouse brain that regulates obesity. The study, which appears ...

Rap1, a potential new target to treat obesity

September 13, 2016
Scientists at Baylor College of Medicine, the National Institutes of Health and Virginia Tech Carilion Research Institute have discovered a new mechanism in the mouse brain that regulates obesity. The study, which appears ...

Recommended for you

Functional engineered oesophagus could pave way for clinical trials 

October 18, 2018
The world's first functional oesophagus engineered from stem cells has been grown and successfully transplanted into mice, as part of a pioneering new study led by UCL.

New findings cast light on lymphatic system, key player in human health

October 16, 2018
Scientists at the Oklahoma Medical Research Foundation have broken new ground in understanding how the lymphatic system works, potentially opening the door for future therapies.

New model suggests cuffless, non-invasive blood pressure monitoring possible using pulse waves

October 16, 2018
A large team of researchers from several institutions in China and the U.S. has developed a model that suggests it should be possible to create a cuffless, non-invasive blood pressure monitor based on measuring pulse waves. ...

Age-related increase in estrogen may cause common men's hernia

October 16, 2018
An age-related increase in estrogen may be the culprit behind inguinal hernias, a condition common among elderly men that often requires corrective surgery, according to a Northwestern Medicine study was published Oct. 15 ...

Income and wealth affect the mental health of Australians, study shows

October 16, 2018
Australians who have higher incomes and greater wealth are more likely to experience better mental health throughout their lives, new research led by the Bankwest Curtin Economics Centre has found.

Discovery of inner ear function may improve diagnosis of hearing impairment

October 15, 2018
Results from a research study published in Nature Communications show how the inner ear processes speech, something that has until now been unknown. The authors of the report include researchers from Linköping University, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.