Neuronal Cell Cycle Events Link Caloric Intake to Obesity

Publication date: Available online 16 October 2019Source: Trends in Endocrinology &MetabolismAuthor(s): Niloy Iqbal, LIang Zhu, Streamson C. ChuaObesity is a neurological disorder that operates by favoring energy storage within adipose depots and increased caloric intake. Most cases of human obesity are acquired without any underlying genetic basis. Here, we suggest that obesity can impair the function of some hypothalamic neurons critical to body weight regulation. Genetic ablation of the retinoblastoma (Rb) gene within pro-opiomelanocortin (POMC) neurons leads to death of the neurons and subsequent obesity. The Rb protein (pRb), a key inhibitor of the cell cycle, can also be inactivated by cyclin dependent kinase (CDK)-mediated phosphorylation. Extensive development led to the production of FDA-approved CDK4/6 inhibitors. Based on our own results, we propose that maintaining or re-instating pRb function using CDK4/6 inhibitors are potentially effective treatments of diet-induced obesity (DIO).
Source: Trends in Endocrinology and Metabolism - Category: Endocrinology Source Type: research

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Abstract Obesity is a neurological disorder that operates by favoring energy storage within adipose depots and increased caloric intake. Most cases of human obesity are acquired without any underlying genetic basis. Here, we suggest that obesity can impair the function of some hypothalamic neurons critical to body weight regulation. Genetic ablation of the retinoblastoma (Rb) gene within pro-opiomelanocortin (POMC) neurons leads to death of the neurons and subsequent obesity. The Rb protein (pRb), a key inhibitor of the cell cycle, can also be inactivated by cyclin dependent kinase (CDK)-mediated phosphorylation. ...
Source: Trends in Endocrinology and Metabolism: TEM - Category: Endocrinology Authors: Tags: Trends Endocrinol Metab Source Type: research
Siriluck Ponsuksili1, Nares Trakooljul1, Frieder Hadlich1, Karen Methling2, Michael Lalk2, Eduard Murani1 and Klaus Wimmers1,3* 1Leibniz Institute for Farm Animal Biology (FBN), Institute for Genome Biology, Functional Genome Analysis Research Unit, Dummerstorf, Germany 2Institute for Biochemistry – Metabolomics, University of Greifswald, Greifswald, Germany 3Faculty of Agricultural and Environmental Sciences, University of Rostock, Rostock, Germany Given the central metabolic role of the liver, hepatic metabolites and transcripts reflect the organismal physiological state. Biochemical-clinical plasma bio...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
ConclusionThese data allowed us to unmask a mechanism by which a KO of p107 prevents diet ‐induced obesity by increasing energy expenditure via increased thermogenesis in BAT and browning of WAT, indicating the relevance of p107 as a modulator of metabolic activity of both brown and white adipocytes. Therefore, it could be targeted for the development of new therapies to ameliorate the metabolic syndrome.This article is protected by copyright. All rights reserved
Source: Molecular Nutrition and Food Research - Category: Food Science Authors: Tags: Research Article Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Today, I'll point out an open access commentary in which the authors survey a number of lines of research into age-related dysfunction in the liver, all of which lead back to elevated levels of cyclin-dependent kinase 4 (CDK4). Some of this work involves investigation of the mechanisms of fatty liver disease, more properly known as hepatic steatosis. This is most commonly caused by being overweight in this age of cheap calories, but, setting aside the morbidly obese, the condition nonetheless tends to emerge later rather than earlier in life. Other research programs look at more directly age-associated measures of liver fu...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Publication date: 19 December 2017 Source:Cell Reports, Volume 21, Issue 12 Author(s): Olivier Goupille, Tipparat Penglong, Zahra Kadri, Marine Granger-Locatelli, Raphaël Denis, Serge Luquet, Cécile Badoual, Suthat Fucharoen, Leila Maouche-Chrétien, Philippe Leboulch, Stany Chrétien GATA transcription factors and their FOG cofactors play a key role in tissue-specific development and differentiation, from worms to humans. Mammals have six GATA and two FOG factors. We recently demonstrated that interactions between retinoblastoma protein (pRb) and GATA-1 are crucial for erythroid proliferation and ...
Source: Cell Reports - Category: Cytology Source Type: research
This study is the first to show that downregulation of PAPP-A expression in adult mice can significantly extend life span. Importantly, this beneficial longevity phenotype is distinct from the dwarfism of long-lived PAPP-A KO, Ames dwarf, Snell dwarf and growth hormone receptor (GHR) KO mice with germ-line mutations. Thus, downregulation of PAPP-A expression joins other treatment regimens, such as resveratrol, rapamycin and dietary restriction, which can extend life span when started in mice as adults. In a recent study, inducible knockdown of the GHR in young adult female mice increased maximal, but not median, lif...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, researchers analysed data of millions of British patients between 1995 and 2015 to see if this claim held true. They tracked people who were obese at the start of the study, defined as people with a body mass index (BMI) of 30 or more, who had no evidence of heart disease, high blood pressure, high cholesterol or diabetes at this point. They found these people who were obese but "metabolically healthy" were at higher risk of developing heart disease, strokes and heart failure than people of normal weight. No such thing as 'fat but fit', major study finds Several studies in the pas...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Obesity is an induced health problem that human beings have been facing with non-optimal treatment so far. Humans are on average getting fatter with age, and obesity and aging interact each other to shorten lifetime and decrease life quality. Obesity also causes several aging related-disorders such as cancer, strokes, cardiovascular disease, high blood pressure and type 2 diabetes. So, the molecular connections between aging and obesity are promising targets for bio-medical researches and innovative therapies of many health problems. In this review, we discuss the findings of adipose p53 and Rb-two centra...
Source: Biogerontology - Category: Geriatrics Authors: Tags: Biogerontology Source Type: research
In conclusion, our data suggest that silencing of DIRAS3 in ASCs and subsequently hyper-activation of Akt-mTOR drives adipogenesis and premature senescence. Moreover, differentiating ASCs and/or mature adipocytes may acquire features of cellular senescence. PMID: 28316325 [PubMed - as supplied by publisher]
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
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