Breaking News
July 21, 2018 - Bundled-payment system did not lower costs for serious medical conditions, shows study
July 21, 2018 - Therapy dogs found to be effective in reducing ADHD symptoms in children
July 21, 2018 - Could rotating multiple therapists better treat PTSD patients?
July 21, 2018 - Binge drinking impairs working memory in adolescent brain
July 21, 2018 - Dying at home could be beneficial for terminally ill cancer patients and their relatives
July 21, 2018 - Researchers identify subtypes of retinal ganglion cells using single-cell RNA sequencing
July 21, 2018 - Study uncovers opportunities to reduce death by suicide among cancer patients
July 21, 2018 - Genetic sequencing reveals new clues to aggressiveness of prostate cancer
July 21, 2018 - BioSight Launches a Phase 2b Clinical Trial of BST-236 as a First-Line Treatment of Acute Myeloid Leukemia
July 21, 2018 - First major study comparing robotic to open surgery published in The Lancet
July 21, 2018 - ADHD medications may fail to improve cognition in healthy college students, study shows
July 21, 2018 - Intervention program that includes a personalized app could benefit teens with suicidal thoughts
July 21, 2018 - Researchers identify new compound that protects against neurodegeneration
July 21, 2018 - Gene therapy may hold potential to treat people with spinal cord injuries
July 21, 2018 - FDA Approves Nivestym (filgrastim-aafi), a Biosimilar to Neupogen
July 21, 2018 - Surgeons have substantial impact on genetic testing in breast cancer patients who need it
July 21, 2018 - Species diversity can have positive and negative impacts on disease transmission
July 21, 2018 - Genome research suggests presence of enteric fever in medieval Europe
July 21, 2018 - Risk of Sensory Deficits Drops With Rising Gestational Age
July 21, 2018 - Mum’s sleep matters—the effect of sleep on an unborn baby
July 21, 2018 - UC San Diego researchers awarded two grants for investigating stem cell-based therapies
July 21, 2018 - Cellular ‘garbage disposal’ may actually work on some of the proteins to neuronal development
July 21, 2018 - More Pregnant Women Having Heart Attacks
July 21, 2018 - Acne Breakouts | NIH News in Health
July 21, 2018 - Change health messaging to focus on potential impact to help stop the next pandemic
July 21, 2018 - Frailty associated with poor survival rates in young heart patients
July 21, 2018 - New discovery could save millions of lives from fatal fungal infections
July 21, 2018 - OBD presents latest data on the use of EpiSwitch™ in predicting patient response to immunotherapy and identifying lymphoma subtypes
July 21, 2018 - Childhood adversity increases susceptibility to addiction via immune response
July 21, 2018 - Scientists identify potential target for the treatment of binge eating
July 21, 2018 - Whole-brain LIPUS therapy improves cognitive dysfunction in mice simulating dementia, Alzheimer’s
July 21, 2018 - Digital media use raising risk of ADHD symptoms among the young
July 21, 2018 - Phase 3 study of tanezumab in patients with osteoarthritis pain meets all three co-primary endpoints
July 21, 2018 - Restoring mitochondrial function to reverse aging-related skin wrinkles, hair loss in mice
July 21, 2018 - SP PennTech introduces RW-500 rotary vial washer for biotech, pharmaceutical applications
July 21, 2018 - Researchers to study molecular mechanisms behind susceptibility of males to autism
July 21, 2018 - Using tendon transfer surgery to restore key functions in spinal cord injury patient
July 21, 2018 - Scientists create wearable device that measures cortisol in sweat
July 21, 2018 - Researchers study efficacy and safety of new treatment for OUD
July 21, 2018 - Fourth Published Clinical Trial Confirms Long-Term Safety of Niagen Supplementation at High Doses and Shows Potential for Improvement in Liver Health
July 21, 2018 - Study examines effects of a two-day intermittent calorie restriction diet for patients with type 2 diabetes
July 21, 2018 - Greening vacant urban land reduces feelings of depression for surrounding residents
July 21, 2018 - Parents say intense gun violence in PG-13 movies appropriate for teens 15 and older
July 21, 2018 - Collaborative study to assess effects of exercise training for cognitive deficits in MS
July 21, 2018 - FAU researchers find possible cause of Parkinson’s disease in the patients’ immune system
July 21, 2018 - Protective qualities of ‘good cholesterol’ reduce after menopause
July 21, 2018 - Researchers develop new way to uncover hidden breast cancer tumors
July 21, 2018 - FDA approves first drug for treatment of adult AML patients with specific genetic mutation
July 21, 2018 - Top AI companies join hands to discover novel drugs for DMD
July 21, 2018 - Ferring announces FDA approval of ZOMACTON for injection in four new pediatric indications
July 20, 2018 - Researchers design proteins that can self-assemble into complex structures
July 20, 2018 - AVITA Medical expands management team to support launch of RECELL device to treat burns
July 20, 2018 - FDA Approves Tibsovo (ivosidenib) for Relapsed or Refractory Acute Myeloid Leukemia with an IDH1 Mutation
July 20, 2018 - Developmental screening and surveillance rates remain low, new study suggests
July 20, 2018 - TGen opens tissue donation portal to advance DIPG research
July 20, 2018 - Health impact of highly processed summertime staples
July 20, 2018 - Exergaming can improve health in overweight and obese children, study shows
July 20, 2018 - Postmenopausal factors may impact heart-protective qualities of ‘good cholesterol’
July 20, 2018 - MRI and blood test combination results in improved prostate cancer diagnosis
July 20, 2018 - Update Health Professional and Consumer on Recent Recalled Products
July 20, 2018 - Researchers trace Parkinson’s damage in the heart
July 20, 2018 - Wearable device designed to measure cortisol in sweat
July 20, 2018 - Scientists demonstrate a new regulation mechanism for skeletal muscles
July 20, 2018 - Exposure to mobile phone radiation may negatively impact memory performance in adolescents
July 20, 2018 - SUSU scientists find alternative method to treat post-traumatic stress disorder syndrome
July 20, 2018 - Gestational diabetes may increase offspring’s heart disease risk
July 20, 2018 - New vaccine could protect unborn babies from Zika virus
July 20, 2018 - Researchers find high mercury and methylmercury concentrations in traditional Tibetan medicine
July 20, 2018 - Brief Safety Plan Intervention in ER Can Cut Suicidal Behavior
July 20, 2018 - The Mount Sinai Hospital receives accreditation as geriatric emergency department
July 20, 2018 - Toward a better understanding of Parkinson’s disease
July 20, 2018 - Med school communications office wins four national awards | News Center
July 20, 2018 - Professional baseball players with faster hand-eye coordination may have better batting performance
July 20, 2018 - Study looks into mechanisms that control sleep and wakefulness
July 20, 2018 - Scientists identify melanoma biomarkers that could help tailor immunotherapy treatments
July 20, 2018 - Research reveals long-term efficacy of drug used to treat common cause of kidney failure
July 20, 2018 - Timing of dinner associated with breast and prostate cancer risks
July 20, 2018 - Health Tip: Performing the Heimlich Maneuver
July 20, 2018 - Nearly all adolescents have eating, activity or weight-related issues
July 20, 2018 - Sage launches new web-based tool that helps explore curated genomic analyses of Alzheimer’s
Brain’s quality control process holds clues to obesity’s roots

Brain’s quality control process holds clues to obesity’s roots

image_pdfDownload PDFimage_print

Deep in the middle of our heads lies a tiny nub of nerve cells that play a key role in how hungry we feel, how much we eat, and how much weight we gain. Around the clock, they produce a “grandfather” form of several hormones that help us regulate these crucial functions.

Now, a new discovery by a team at the University of Michigan Medical School sheds new light on how that grandfather molecule gets produced – and more important, what can go wrong and raise the risk of overeating and obesity.

Published online in the Journal of Clinical Investigation, the findings could pave the way for new approaches to treating forms of obesity, especially those with genetic roots. They also improve the understanding of how the body controls the levels of hormones related to appetite and much more.

ERAD: A key protein quality control mechanism

The grandfather hormone, or prohormone, is called pro-opiomelanocortin or POMC. After it’s produced by the cells in the region of the brain called the hypothalamus, it gets chopped up to make several important appetite-regulating hormones.

But the new research shows that before POMC can leave the cells that produce it, every single copy has to pass a kind of inspection. This ensures that poorly made POMC copies get cleared in a timely way.

It’s a process called ERAD, for endoplasmic reticulum-associated protein degradation

The researchers show that the ERAD process in POMC neurons controls food intake and obesity by tightly regulating the amount of POMC released by the cells. If ERAD fails, their experiments showed, most POMC molecules get clumped up and held inside the cell. That means far fewer appetite-regulating hormone molecules reaching the body.

The U-M experiments showed that mice with a broken ERAD system in their POMC neurons ate far more than usual, and gained weight rapidly, becoming obese – even though they were fed a low-energy diet.

“Our findings demonstrate that, surprisingly but unequivocally, the ERAD machinery plays a key role in normal physiology,” say Ling Qi, Ph.D., a professor in the U-M Department of Molecular & Integrative Physiology who led the team. “These new revelations identify new elements in disease pathogenesis, and will help us design novel therapeutic approaches and targets for preventing and treating obesity.”

ERAD in human obesity

Knowing that a rare, severe form of childhood obesity arises from a mutation in the POMC gene, the researchers explored the relationship between ERAD and this mutation.

Humans with the mutation, called C28F, feel constant hunger and have complete lack of control over eating. They become severely obese in their early years.

The researchers found that mutated POMC molecules evade the ERAD quality control process and built up inside of the brain cells where they were made – getting in the way of the production of normal POMC.

Both cases -; the mice with broken ERAD, and the patients with mutated POMC -; surprisingly share the same underlying reasons: the built-up misfolded POMC molecules clump together and keep the entire hormone factory from running smoothly.

Strangely, the buildup didn’t cause the cells to die. They just didn’t pump out the POMC prohormone.

The researchers, including lead author Geun Hyang Kim, Ph.D., a postdoctoral fellow in the Qi lab, conclude that properly functioning ERAD provides a “safe space” for the cell to put finishing touches on its products, keeping the bad proteins from clumping together with the good ones.

This opens the door to new experiments with drugs that could boost the ERAD process in POMC-producing brain cells.

Exploring ERAD’s role in other prohormones

The researchers focused on POMC-producing cells in the brain region called the arcuate nucleus of the hypothalamus, and a pair of ERAD quality control molecules called Sel1L-Hrd1.

Qi and his colleagues last year showed that problems with ERAD affect production of another prohormone, proAVP, which is the grandfather of a hormone called vasopressin that regulates water balance in the body. Mice lacking ERAD in vasopressin-producing neurons develop a condition called diabetes insipidus, just like humans with the same condition.

“Whenever you generate mice exhibiting human disease-like phenotypes, you know you are working on something with fundamental importance,” he says. “The ultimate question for us is, can we manipulate this system to treat human diseases.”

For instance, he says, using the knowledge gained from these studies, a small-molecule drug might be developed to boost the activity of the ERAD machinery, to make sure prohormones gets handled correctly. The team is working with other U-M colleagues to test some of these ideas.

Source:

https://labblog.uofmhealth.org/lab-report/clues-to-obesitys-roots-found-brains-quality-control-process

Tagged with:

About author

Related Articles