Breaking News
February 23, 2019 - Surprise rheumatoid arthritis discovery points to new treatment for joint inflammation
February 23, 2019 - A just-right fix for a tiny heart
February 23, 2019 - Owlstone Medical and Shanghai Renji Hospital collaborate to initiate breath biopsy lung cancer trial
February 23, 2019 - AMSBIO’s comprehensive portfolio of knock-out cell lines and lysates
February 23, 2019 - New app reliably determines physicians’ skills in forming accurate, efficient diagnoses
February 23, 2019 - Peripheral nerve injury can trigger the onset and spread of ALS, shows study
February 23, 2019 - Researchers uncover mechanisms that prevent tooth replacement in mice
February 23, 2019 - Once-a-day capsule offers new way to reduce symptoms of chronic breathlessness
February 23, 2019 - FDA Adds Boxed Warning for Increased Risk of Death with Gout Medicine Uloric (febuxostat)
February 23, 2019 - Phone-based intervention aids rheumatoid arthritis care
February 23, 2019 - Opioid epidemic makes eastern inroads and targets African-Americans
February 23, 2019 - New identified biomarker predicts patients who might benefit from HER2-targeted agents
February 23, 2019 - Study offers new insights into mechanisms of changes in erythrocytes under stress
February 23, 2019 - Antipsychotic polypharmacy may be beneficial for schizophrenia patients
February 23, 2019 - Researchers investigate how marijuana and tobacco co-use affects quit attempts by smokers
February 23, 2019 - Patients with diabetes mellitus have high risk of stable ischemic heart disease
February 23, 2019 - Transparency on healthcare prices played key role in Arizona health system’s turnaround
February 23, 2019 - A comprehensive, multinational review of peppers around the world
February 23, 2019 - Study finds modest decrease in burnout among physicians
February 23, 2019 - A simple change can drastically reduce unnecessary tests for urinary tract infections
February 23, 2019 - Deep Learning-Enhanced Device Detects Diabetic Retinopathy
February 23, 2019 - Researchers discover new binding partner for amyloid precursor protein
February 23, 2019 - Modest decrease seen in burnout among physicians, researchers say | News Center
February 23, 2019 - Transplanting bone marrow of young mice into old mice prevents cognitive decline
February 23, 2019 - Mogrify to accelerate novel IP and cell therapies using $3.7m USD funding
February 23, 2019 - Johns Hopkins study describes cells that may help speed bone repair
February 23, 2019 - Scientists demonstrate influence of food odors on proteostasis
February 23, 2019 - Researchers unlock the secret behind reproduction of fish called ‘Mary’
February 23, 2019 - Acupuncture Could Help Ease Menopausal Symptoms
February 23, 2019 - Researchers use AI to detect early signs of Alzheimer’s
February 23, 2019 - On recovery, vulnerability and ritual: An exhibit in white | News Center
February 23, 2019 - Memory Stored in Unexpected Region of the Brain
February 23, 2019 - Several health experts worldwide gather at EUDONORGAN event
February 23, 2019 - Discovery of potent compound in native California shrub may lead to treatment for Alzheimer’s
February 22, 2019 - Researchers create new map of the brain’s own immune system
February 22, 2019 - ICHE’s reviews on surgical infections, unnecessary urine tests, and nurses’ role in antibiotic stewardship
February 22, 2019 - UK Research and Innovation invests £200 million to create new generation of AI leaders
February 22, 2019 - Takeda collaboration to boost fight against Alzheimer’s and other neurodegenerative diseases
February 22, 2019 - Heavy drinking may change DNA, leading to increased craving for alcohol
February 22, 2019 - U.S. opioid deaths jump fourfold in 20 years; epidemic shifts to Eastern states | News Center
February 22, 2019 - 5 Questions with William Turner on Diversity in Medicine
February 22, 2019 - HHS Finalizes Rule Seeking To Expel Planned Parenthood From Family Planning Program
February 22, 2019 - Researchers uncover biochemical pathway that may help identify drugs to treat Alzheimer’s
February 22, 2019 - Biologist uses new grant to find ways to eliminate schistosomiasis
February 22, 2019 - Bag-mask ventilation to help patients breathe during intubation prevents complications
February 22, 2019 - AbbVie Announces New Drug Application Accepted for Priority Review by FDA for Upadacitinib for Treatment of Moderate to Severe Rheumatoid Arthritis
February 22, 2019 - Nature versus nurture and addiction
February 22, 2019 - New website connects researchers with data experts, resources | News Center
February 22, 2019 - Today’s Concerns About Drug Prices Echo The Past
February 22, 2019 - CT and Doppler equipment have low accuracy in detecting cerebral vasospasm and ischemia
February 22, 2019 - Study finds out similarity in function between healthy retina cell and tumor cell
February 22, 2019 - CWRU awarded NIH grant to identify effective treatments for intimate partner violence
February 22, 2019 - Oncotype DX Not Cost-Effective for Low-Risk Breast Cancer
February 22, 2019 - Scientists discover new type of immune cells that are essential for forming heart valves
February 22, 2019 - Talk About Déjà Vu: Senators Set To Re-Enact Drug Price Hearing Of 60 Years Ago
February 22, 2019 - Genetic defect linked to pediatric liver disease identified
February 22, 2019 - New cellular atlas could provide a deeper insight into blinding diseases
February 22, 2019 - Growing number of cancer survivors, fewer providers point to challenge in meeting care needs
February 22, 2019 - Innovative compound offers a new therapeutic approach to treat multiple sclerosis
February 22, 2019 - $1.5 million grant to develop opioid treatment program for jail detainees
February 22, 2019 - FDA’s new proposed rule would update regulatory requirements for sunscreen products in the U.S
February 22, 2019 - Most Hip, Knee Replacements Last Decades, Study Finds
February 22, 2019 - Wellness problems prevalent among ob-gyn residents
February 22, 2019 - In the Spotlight: “The world is your oyster in geriatrics”
February 22, 2019 - Successful testing of multi-organ “human-on-a-chip” could replace animals as test subjects
February 22, 2019 - Analysis of cervical precancer shows decline in two strains of HPV
February 22, 2019 - Sugary stent eases suturing of blood vessels
February 22, 2019 - From surgery to psychiatry: A medical student reevaluates his motivations
February 22, 2019 - Is New App From Feds Your Answer To Navigating Medicare Coverage? Yes And No
February 22, 2019 - New pacemakers powered by heartbeats could reduce need for surgery
February 22, 2019 - The United States records highest drug overdose death rates
February 22, 2019 - Heart attacks more likely to be fatal in women and rates are rising
February 22, 2019 - Morning walks could be better than drugs at lowering blood pressure
February 22, 2019 - Phase 1 data reinforce safety profile of new drug for treating Duchenne muscular dystrophy
February 22, 2019 - Vitamin D supplementation less effective in the presence of obesity, shows study
February 22, 2019 - Novostia raises CHF 6.5 million to advance its aortic, mitral heart valve to clinical trials
February 22, 2019 - CPRIT awards nearly $20 million to The University of Texas MD Anderson Cancer Center
February 22, 2019 - Sarepta Announces FDA Acceptance of Golodirsen (SRP-4053) New Drug Application for Patients with Duchenne Muscular Dystrophy Amenable to Skipping Exon 53
February 22, 2019 - An institutional effort to reduce the amount of opioids prescribed following lumbar surgery
February 22, 2019 - Family-history-based models perform better than non-family-history based models
Diet-induced obesity synchronizes opposing liver fat metabolic processes in mice

Diet-induced obesity synchronizes opposing liver fat metabolic processes in mice

image_pdfDownload PDFimage_print

Mice fed a fattening diet develop new liver circadian rhythms that impact the way fat is accumulated and simultaneously burned, according to a new study published in Cell by researchers in the Perelman School of Medicine at the University of Pennsylvania. The team found that as liver fat production increases, surprisingly, so does the body’s ability to burn fat. These opposing physiological processes reach their peak activity each day around 5 p.m., illustrating an unexpected connection between overeating, circadian rhythms, and fat accumulation in the liver.

“We know that obesity leads to accumulation of fat in the liver, which can cause inflammation and possibly hepatitis, liver failure, and even liver cancer,” said senior author Mitchell Lazar, MD, PhD, director of Penn’s Institute for Diabetes, Obesity, and Metabolism, and chief of the division of Endocrinology, Diabetes and Metabolism. “This is rapidly becoming a huge problem, as these conditions can lead to an increased need for liver transplantation, and worse, can be deadly.”

While one billion people worldwide are adversely affected by malnutrition, there are another billion who experience excess calorie intake, or “overnutrition,” which leads to obesity and other metabolic disorders including type-2 diabetes, cardiovascular disease, fatty liver, hypertension, and cancer. “Studying the harmful effects of overnutrition is a top priority, especially in the United States where metabolic disorders have reached epidemic proportions,” Lazar said.

The circadian rhythms that fat creation and burning follow are physiological processes that occur with about every 24 hours. At the molecular level, these cycles involve feedback loops of core clock proteins expressed in virtually every cell of the body. This internal timekeeper functions to integrate environmental stimuli and genetic information to control rhythmic gene expression in a tissue-specific way.

A misalignment of this schedule is increasingly recognized as a risk factor for metabolic disorders. For example, night shift workers and individuals with sleep disorders have an increased risk of metabolic diseases. Understanding the mechanisms that impact the relationship between circadian rhythms and metabolic disorders are necessary for the development of meaningful therapeutic strategies for treating obesity-related diseases.

“We speculate that the diet-induced synchronization of these opposing liver fat metabolic processes is a response to an environment of overnutrition, leading to fat burning outpacing fat accumulation in the liver,” said first author Dongyin Guan, PhD, a postdoctoral fellow in Lazar’s lab.

The 24-hour clock aspect of this physiology informs the practice of chronotherapy, which involves administering drugs at times when they are most impactful and tolerated in order to enhance effectiveness and reduce toxicity. The team discovered that the rhythm of fat burning is controlled by a protein called PPAR-alpha, which is the target of drugs called fibrates, which are already used to lower lipids in the blood. The amount of PPAR-alpha in the liver also peaked around 5 p.m.

From this coordination, Lazar’s team asked whether there would be a benefit to giving short-acting PPAR-alpha drugs at the specific time of day when PPAR-alpha is at its highest level. The researchers observed that a short-acting PPAR-alpha drug reduced liver fat more when it was given in the afternoon than when it was given in the morning.

Similar to how statins (cholesterol-lowering drugs) are prescribed to be taken at bedtime, “our results support that due to the rhythmicity of PPAR-alpha, drugs that lower liver and blood lipid levels could be more effective at specific times of day,” Lazar said. “Following this principle more closely to treat liver metabolic disease may indeed benefit patients, as recent studies have shown that PPAR-alpha expression oscillates in the human liver.”

Source:

https://www.pennmedicine.org/news/news-releases/2018/july/fat-production-and-burning-are-synchronized-in-livers-of-mice-with-obesity-penn-study-finds

Tagged with:

About author

Related Articles