High-fat diet (HFD) feeding in mice promotes induction of aldose reductase (AR) activity, expression, and senescence of adipocytes in subcutaneous adipose tissue (scAT), according to a new study inObesity. The researchers, headed by a New York University Grossman School of Medicine team, suggest that their findings could point to potential new strategies for treating obesity. Our data demonstrate that aldose reductase gene expression increases in scAT of obese humans and mice, and that an inhibitor of aldose reductase attenuates weight gain, reduces adipocyte senescence, and promotes lipolysis in HFD-fed mice, said Ravichandran Ramasamy, PhD, professor, diabetes research program, department of medicine, NYU Grossman School of Medicine. These data pave the way for testing these inhibitors as therapeutic adjuncts in treating patients with obesity.
Ramasamy is corresponding author of the teams study, which is titled, Aldose reductase promotes diet-induced obesity via induction of senescence in subcutaneous adipose tissue, and in which they concluded, These data unveil new opportunities to target these pathways to combat obesity.
Senescence is a state of permanent proliferative cell cycle arrest, the authors noted, which occurs in cells exposed to a variety of stresses. In HFD-induced models of obesity, various cell types, including adipocytes, immune cells, neuronal cells, and osteoprogenitors, have been shown to undergo senescence, they further commented. Although adipose tissue senescence has been observed in humans with obesity and in mouse models of obesity, the pathways driving this process are unclear.
In their newly reported study, Ramasamy and colleagues identified a novel role for the enzyme aldose reductase (akr1b3 in mice, and AKR1B1 in humans) in response to high-fat feeding in mice. Their studies showed that AR promotes induction of senescence in subcutaneous inguinal white adipose tissue in wild-type (WT) mice fed a high-fat diet.
To determine whether the AR pathway affected obesity in HFD-fed mice, and to establish its relationship to senescence and lipolysis, WT mice were fed an HFD for 11 weeks, followed by three weeks of continued HFD, plus treatment using either the AR inhibitor (ARI) zopolrestat (zop) or vehicle (potassium bicarbonate buffer used to dissolve zop). All the animals were male, had free access to water and food, and were subjected to 12-hour light/dark cycles. For a study in human subjects, researchers obtained cDNA samples of subcutaneous fat from fasted lean and fasted subjects with obesity.
The study results showed that in animals fed an HFD there was a significant increase in AR and the senescence marker Cdkn2a expression in all tissues, when compared with results in mice fed normal chow. Glycerol, non-esterified free fatty acid (NEFA), and triglycerides measured from plasma after a four-hour fast revealed significantly higher NEFA levels in HFD-fed mice when compared with the chow-fed mice. Analysis of cDNA samples from human subjects with obesity showed also increased expression of AR and senescence marker.
Increased expression of aldose reductase and senescence in the adipose tissue of humans and mice with obesity were demonstrated, the team wrote. In the animals given the aldose reductase inhibitor, zop, however, the collective data suggested thatthe treatment enhanced lipolysis and attenuated HFD-induced weight gain and scAT senescence.
Separately, the team carried out an analysis of Akr1b3 knockdown mice (Akr1b3-/- animals) that were fed an HFD. The resulting data also indicated that Akr1b3-/- HFD-fed mice are protected from HFD-induced obesity and that protection is linked to attenuation of senescence markers and enhanced adrenergic pathway-driven lipolysis in scAT, the authors noted. Genetic deletion of Akr1b3 or pharmacological blockade of AKRIB3 with zopolrestat reduced HFD-induced obesity, attenuated markers of adipose tissue senescence, and increased lipolysis.
They concluded, AKR1B1/Akr1b3 modulation of senescence in subcutaneous adipose tissue contributes to aberrant metabolic responses to high-fat feeding Our data demonstrate that AR gene expression increases in subcutaneous adipose tissue of humans and mice with obesity and that an inhibitor of AR attenuates weight gain, reduces senescence, and promotes lipolysis in HFD-fed mice; these data pave the way for the testing of these inhibitors as therapeutic adjuncts in treating patients with obesity.
AdventHealth senior vice president and CSO Steven R. Smith, MD, an expert in this areathough not linked to the reported researchfurther commented, This is an important discovery, and the data is compelling. Today, we dont have good medicines that target dysfunctional adipose tissue. Im very excited by this work; these findings should compel scientists to find drugs that impact this novel pathway and could be used to treat both obesity and diabetes.
See original here:
Enzyme that Promotes Diet-Induced Obesity Could Point to Inhibitor Therapy - Genetic Engineering & Biotechnology News
- Viewpoint: Anti-GMO arguments seem silly after 28 years of false narratives about health harms and and genetic ... - Genetic Literacy Project - March 29th, 2024 [March 29th, 2024]
- Viewpoint: Here's how genetically engineered fruits and vegetables will soon emerge as a grocery store 'selling point ... - Genetic Literacy Project - March 29th, 2024 [March 29th, 2024]
- CRISPR Investments: What We Heard at World Agri-Tech - Seed World - March 29th, 2024 [March 29th, 2024]
- When SpaceX's Starship is ready to settle Mars, will we be? (op-ed) - Space.com - September 17th, 2023 [September 17th, 2023]
- Genome-wide promoter responses to CRISPR perturbations of ... - Nature.com - September 17th, 2023 [September 17th, 2023]
- Expanding the toolbox for RNA editing | ASU News - ASU News Now - September 17th, 2023 [September 17th, 2023]
- Electrical Engineer Named MIT Technology Review Innovator Under ... - University of California San Diego - September 17th, 2023 [September 17th, 2023]
- Can we rely on our 'moral force-field' to stop cloning going too far? - The National - September 17th, 2023 [September 17th, 2023]
- Otsuka Collaborates with ShapeTX for Development of AAV Gene ... - Pharmaceutical Technology Magazine - September 17th, 2023 [September 17th, 2023]
- Cancer discovery earns U of A grad the Breakthrough Prize - University of Alberta - September 17th, 2023 [September 17th, 2023]
- The Brave New World of synthetic humans | Gne Taylor - IAI - September 17th, 2023 [September 17th, 2023]
- Targeting Tumors with Photosynthetic Bacteria - Optics & Photonics News - September 17th, 2023 [September 17th, 2023]
- Artificial Photosynthesis Breakthrough Researchers Produce ... - SciTechDaily - September 17th, 2023 [September 17th, 2023]
- BASF patent on watermelons upheld: European Patent Office rejects ... - Bio Eco Actual - September 17th, 2023 [September 17th, 2023]
- Space Industry Is Growing Faster Than Its Workforce, Analysts Say - Slashdot - September 17th, 2023 [September 17th, 2023]
- New 'Inverse Vaccine' Shows Potential to Treat MS and Other ... - Slashdot - September 17th, 2023 [September 17th, 2023]
- Gene therapy: Donor DNA may protect babies from certain disorders - Medical News Today - May 18th, 2023 [May 18th, 2023]
- Viewpoint: Grim consequences of Greenpeace's war on ... - Genetic Literacy Project - May 18th, 2023 [May 18th, 2023]
- Predicting Diabetic Kidney Disease with the Use of a Novel Algorithm - Genetic Engineering & Biotechnology News - May 18th, 2023 [May 18th, 2023]
- Quantum biology on horizon? How futuristic physics theory could ... - Study Finds - May 18th, 2023 [May 18th, 2023]
- Scientists can collect human DNA from water, air, and basically ... - Earth.com - May 18th, 2023 [May 18th, 2023]
- The First Crispr-Edited Salad Is Here - WIRED - May 18th, 2023 [May 18th, 2023]
- Gene editing technology used to produce disease-resistant calf - Earth.com - May 18th, 2023 [May 18th, 2023]
- Neanderthals passed down their tall noses to modern humans ... - Livescience.com - May 18th, 2023 [May 18th, 2023]
- Squid Camouflage Inspires Human Invisibility: Is it Possible? - DISCOVER Magazine - May 18th, 2023 [May 18th, 2023]
- Mice Model Technologies Market Poised for 7.4% CAGR Growth, Reaching USD 3.2 Bn by 2031 | Transparency Market Research - Yahoo Finance - May 18th, 2023 [May 18th, 2023]
- Google Cloud launches A.I.-powered tools to accelerate drug discovery, precision medicine - CNBC - May 18th, 2023 [May 18th, 2023]
- How Fauci, scientists with ties to Wuhan lab persuaded the ... - U.S. Right to Know - May 18th, 2023 [May 18th, 2023]
- The Daunting Task of Cutting Heavy Metals from Baby Food - Undark Magazine - May 18th, 2023 [May 18th, 2023]
- Ingestible Device Profiles and Peers into the Microbiome and ... - Genetic Engineering & Biotechnology News - May 18th, 2023 [May 18th, 2023]
- X-Men Officially Names the Best Powers Any Mutant Can Have - Screen Rant - May 18th, 2023 [May 18th, 2023]
- 10 Forgotten Marvel Comics Characters That Debuted In The '80s - Screen Rant - May 18th, 2023 [May 18th, 2023]
- 18 Human Genetic Engineering - Clemson University - April 19th, 2023 [April 19th, 2023]
- Pros and Cons of Genetic Engineering - Benefits and Risks - March 31st, 2023 [March 31st, 2023]
- What is Genetic Engineering? Types, Process & Applications - March 31st, 2023 [March 31st, 2023]
- How artificial skin is made and its uses, from treating burns to skin cancer - South China Morning Post - March 31st, 2023 [March 31st, 2023]
- Welcome to the UNC Department of Genetics | Department of Genetics - February 5th, 2023 [February 5th, 2023]
- Global Genetically Modified Crops Market Is Projected To Grow At A 6% Rate Through The Forecast Period - EIN News - February 5th, 2023 [February 5th, 2023]
- Science and History of GMOs and Other Food Modification Processes - February 2nd, 2023 [February 2nd, 2023]
- Genetics | History, Biology, Timeline, & Facts | Britannica - January 31st, 2023 [January 31st, 2023]
- Human genetics | Description, Chromosomes, & Inheritance - January 31st, 2023 [January 31st, 2023]
- Genetic testing - Mayo Clinic - January 31st, 2023 [January 31st, 2023]
- Genetic Disorders: What Are They, Types, Symptoms & Causes - January 31st, 2023 [January 31st, 2023]
- Colossal Biosciences Project to Revive the Prehistoric Woolly Mammoth Raises Staggering $60 Million Series A Funding - Nature World News - January 22nd, 2023 [January 22nd, 2023]
- 2023 is going to witness a surge in technology courses top courses that will remain in vogue - Times of India - January 22nd, 2023 [January 22nd, 2023]
- M.R.S. Rao birthday: All you need to know about the Padma Shri winning Indian scientist - Free Press Journal - January 22nd, 2023 [January 22nd, 2023]
- Russian cosmism - Wikipedia - January 8th, 2023 [January 8th, 2023]
- Postgenderism - Wikipedia - January 8th, 2023 [January 8th, 2023]
- LessWrong - Wikipedia - January 8th, 2023 [January 8th, 2023]
- Eliezer Yudkowsky - Wikipedia - January 8th, 2023 [January 8th, 2023]
- Genetic Engineering Principles of Biology - December 26th, 2022 [December 26th, 2022]
- Engineering the Perfect Baby | MIT Technology Review - December 26th, 2022 [December 26th, 2022]
- Genetic Engineering Science Projects - Science Buddies - December 21st, 2022 [December 21st, 2022]
- DSI adoption at COP15 can financially help protect biodiversity in India: Experts - The Tribune India - December 21st, 2022 [December 21st, 2022]
- Tel Aviv University researchers demonstrate success of potential one-time vaccine to treat HIV/AIDS - ETHealthWorld - December 21st, 2022 [December 21st, 2022]
- Should You Buy 22nd Century Group Inc (XXII) Stock After it Has Risen 14.29% in a Week? - InvestorsObserver - October 28th, 2022 [October 28th, 2022]
- Home :: National Institute for Biotechnology and Genetic Engineering - October 11th, 2022 [October 11th, 2022]
- A recently discovered law of physics could help predict genetic mutations - October 11th, 2022 [October 11th, 2022]
- Farmers, consumers will embrace GMOs if they understand them - The Standard - October 11th, 2022 [October 11th, 2022]
- Synthetic Biology Market is Expected to Report a CAGR of ~21% from 2021 to 2029: Industry Size, Growth & Forecast at Douglas Insights - Yahoo... - October 11th, 2022 [October 11th, 2022]
- After 45 years of science-based art, Esther Klein Gallery winds down - WHYY - October 11th, 2022 [October 11th, 2022]
- Behind this Nobel prize is a very human story: theres a bit of Neanderthal in all of us - The Guardian - October 11th, 2022 [October 11th, 2022]
- The key to tastier beer might be mutant yeastwith notes of banana - Popular Science - October 11th, 2022 [October 11th, 2022]
- Why You'll Probably Never See Cotton Candy Grape Wine - Tasting Table - October 11th, 2022 [October 11th, 2022]
- Earth materials in technology The National - The National - October 11th, 2022 [October 11th, 2022]
- CULINARY THRILL SEEKING Proceed with caution. It's hotter than blazes season. - Port Arthur News - The Port Arthur News - October 11th, 2022 [October 11th, 2022]
- Give legal rights to animals, trees and rivers, say experts - The Guardian - October 11th, 2022 [October 11th, 2022]
- How yeast DNA may help protect astronauts from cosmic radiation in space - EastMojo - October 11th, 2022 [October 11th, 2022]
- Life finds a way, but should it? The ethics of genetic engineering - The Trinitonian - October 8th, 2022 [October 8th, 2022]
- To modify or not to modify? Genetic Modification and Gene Editing - A divergence by the UK - Lexology - October 8th, 2022 [October 8th, 2022]
- Gene Therapy Hits Its Stride in the Clinic - Genetic Engineering & Biotechnology News - October 8th, 2022 [October 8th, 2022]
- GWAS, MWAS and mGWAS provide insights into precision agriculture based on genotype-dependent microbial effects in foxtail millet - Nature.com - October 8th, 2022 [October 8th, 2022]
- Making Sense of the Latest Apple-iPhone News - The Motley Fool - October 8th, 2022 [October 8th, 2022]
- Gene therapy brings hope to people with sickle cell, HIV - Monitor - October 8th, 2022 [October 8th, 2022]
- GMO: Everything you need to know about lifting ban - FarmKenya Initiative - The Standard - October 8th, 2022 [October 8th, 2022]
- Century Therapeutics to Present at the SITC 37th Annual Meeting - Yahoo Finance - October 8th, 2022 [October 8th, 2022]
- Cultured meat could help solve the climate crisis. Heres what it will take to move it from the lab to the dinner table - Fortune - October 8th, 2022 [October 8th, 2022]
- Poseida Therapeutics to Present Trial in Progress Poster for Phase 1 P-MUC1C-ALLO1 Study at the Society for Immunotherapy of Cancer Annual Meeting -... - October 8th, 2022 [October 8th, 2022]
- Explained: How scientists engineered mosquitoes that will cut the transmission of malaria - Firstpost - October 8th, 2022 [October 8th, 2022]
- Here Are the Biggest Health Industry News Items of 2022 So Far - DocWire News - October 8th, 2022 [October 8th, 2022]