Genes Help Determine Whether You Are Shaped Like an Apple or Pear

MedicalResearch.com Interview with:

Ruth Loos, PhD The Charles Bronfman Professor in Personalized Medicine Director, Genetics of Obesity and Related Traits Program Co-Director, Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai New York, NY

Dr. Loos


Ruth Loos, PhD
The Charles Bronfman Professor in Personalized Medicine
Director, Genetics of Obesity and Related Traits Program
Co-Director, Charles Bronfman Institute for Personalized Medicine
Icahn School of Medicine at Mount Sinai
New York, NY

 

 

MedicalResearch.com: What is the background for this study? Which type of body fat distribution carries greater risk of diabetes or other obesity-related health disorders?

Response: Obesity broadly consists of two component; [1] there is overall body size (assessed using BMI) and [2] there is fat distribution (assessed using WHR). Both are “heritable”, which mean that they are in part determined by our genome (and the other part is determined by our lifestyle).

Over the past 15 years, geneticists have used an approach to screen the whole genome of thousands of people to identify genetic variations that differ between e.g. obese people vs non-obese people.

We have applied this approach to both components of obesity and have found so far that genes for “overall body size” seem to act in the brain, likely controlling hunger, satiety, reward, etc., whereas the genes that determine where in the body the excess fat will be stored when you gain weight (i.e. fat distribution) seem to act more “locally” at the fat cell level itself, determining the storage and release of fat.  Continue reading

Adiposity Related Cancer Risk May Vary On Fat Locations

MedicalResearch.com Interview with:
Arjun Gupta, MD and

Ian J. Neeland MD, Assistant Professor
Dedman Family Scholar in Clinical Care
Division of Cardiology
UT Southwestern Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Adiposity is traditionally measured using the body mass index, which refers to a persons weight in kilograms divided by their height (in meters) squared. Persons with higher body mas index have been shown to have increased risk of certain cancers, however body mass index by itself is not a completely representative measure of body fat risk, because distinct fat depots such as visceral adipose tissue, abdominal subcutaneous adipose tissue, liver fat and lower body fat have differing metabolic impact.

We aimed to study the relationship between specific fat depots and the risk of incident cancer among relatively young, multiethnic participants in the Dallas Heart Study. Individuals without prevalent cancer underwent quantification of adipose depots using MRI and DEXA scans from 2000-2002, and were followed for the development of cancer for up to 12 years. In multivariable models adjusted for age, sex, race, smoking, alcohol use, family history of malignancy and body mass index, visceral adipose tissue, subcutaneous adipose tissue or liver fat were not associated with risk of cancer but each 1-standard deviation increase in lower body fat was associated with a 31% reduced incidence of cancer.

Continue reading

Newly Identified Molecule Turns Fat Storage Gene Off

MedicalResearch.com Interview with:

Prof. Jamal Tazi Institut de Génétique Moléculaire de Montpellier University of Montpellier Montpellier, Cedex, France

Prof. Jamal Tazi

Prof. Jamal Tazi
Institut de Génétique Moléculaire de Montpellier
University of Montpellier
Montpellier, Cedex, France

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. In this study we have used a novel approach to uncover novel drugs to treat obesity. Our approach is based on the finding that in humans the energy expenditure balance can be controlled by a single gene LMNA gene that can produce two different proteins with opposing effect on energy expenditure. We identified a molecule ABX300 that targets the expression of LMNA gene and favors energy expenditure leading to fat loss.

Continue reading

Byproduct of Sweet Potato Waste Offers Clue To Lipid Metabolism

MedicalResearch.com Interview with:
Dr. Koji Ishiguro

National Agriculture and Food Research Organization
Japan

MedicalResearch.com: What is the background for this study?

Response: -Sweet potato (Ipomoea batatas L.) roots are not only used for human consumption, they are used to make starch materials, processed foods, and distilled spirits in Japan. Starch use accounts for about 15% (131,500 tons) of total sweet potato production. Starch residues are discharged during starch production and are mainly used in animal feed and compost. Large amounts of the wastewater, which can cause serious environmental problems, are discarded after clarification. Investigation into the uses of the by-products of the sweet potato starch industry would benefit both the environment and industry.

Continue reading

Genes Linked To Ectopic Fat Deposition Identified

MedicalResearch.com Interview with:

Audrey Chu, Ph.D. Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health

Dr. Audrey Chu

Audrey Chu, Ph.D.
Division of Intramural Research
National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Body shape reflects the underlying adipose tissue distributed throughout different compartments of the body (ectopic fat). Variation in ectopic fat is associated with diabetes, hypertension and heart disease. This is mostly independent of overall adiposity. Ectopic fat can be measured using special x-rays procedures such as CT (“CAT scans”) or MRI and can give more information about fat distribution. Fat distribution characteristics can run in families, suggesting that a person’s genes can help determine the amount of fat that can accumulate in different parts of the body. Identifying genes that are associated with ectopic fat can provide insight into the biological mechanisms leading to differences in cardiometabolic disease risk.

In order to understand which genes might be involved, we examined genetic variants across the genome and their association with ectopic fat in the largest study of its kind including over 18,000 individuals of four different ancestral backgrounds.

Several new genetic regions were identified in association with ectopic fat in addition to confirming previously known regions. The association of the new regions was specific to ectopic fat, since the majority of the regions were not associated with overall or central adiposity. Furthermore, most of these regions were not associated with type 2 diabetes, lipids, heart disease or blood pressure. The major exception was the region surrounding the UBE2E2 gene, which was associated with diabetes.

Continue reading

High Dietary Saturated Fat Associated With Prostate Cancer Aggressiveness

MedicalResearch.com Interview with:

Emma Helen Allott, PhD University of North Carolina at Chapel Hill Chapel Hill, NC

Dr. Emma Allott

Emma Helen Allott, PhD
University of North Carolina at Chapel Hill
Chapel Hill, NC

MedicalResearch.com: What is the background for this study?

Dr. Allott: Prostate cancer incidence rates vary more than 25-fold worldwide, and are highest in Western countries. This large international variation is due in part to differences in screening practices between countries, but dietary factors may also play a role. Unlike other macronutrients, dietary fat intake varies more than fivefold worldwide, and individuals in Western countries are among the highest consumers of saturated fat. High dietary saturated fat content contributes to raised blood cholesterol levels, and evidence from population-based studies supports an adverse role for serum cholesterol and a protective role for cholesterol-lowering statins in prostate cancer. Our hypothesis in this study was that high saturated fat intake would drive prostate tumor aggressiveness via raising serum cholesterol levels.

MedicalResearch.com: What are the main findings?

Dr. Allott: Using the North Carolina-Louisiana Prostate Cancer Project, a study of 1,854 men with newly-diagnosed prostate cancer, we show that high dietary saturated fat content is associated with increased tumor aggressiveness. We found a slightly weaker effect of saturated fat on prostate cancer aggressiveness in men using statins to control serum cholesterol levels, suggesting that that statins may counteract, but do not completely negate, the effects of high saturated fat intake on prostate cancer aggressiveness. We also found an inverse association between high dietary intake of polyunsaturated fatty acids (PUFAs) and prostate cancer aggressiveness.

Continue reading

Synthetic Growth Hormone Releaser May Reduce Excess Abdominal Fat in HIV Patients

Julian Falutz, MD Director, HIV Metabolic Clinic MUHC,  Coordinator of Chronic Viral Illness Service, HIV and Aging Clinic McGill University Health Center

Dr. Julian Falutz

MedicalResearch.com Interview with:
Julian Falutz, MD

Director, HIV Metabolic Clinic MUHC,
Coordinator of Chronic Viral Illness Service, HIV and Aging Clinic
McGill University Health Center

Medical Research: What is the background for this study? What are the main findings?

Dr. Falutz: The long-term use of antiretroviral therapy (ART) in HIV-infected patients is associated with body composition changes, including visceral adipose tissue (VAT) accumulation. HIV-infected patients with excess VAT may be at increased risk of type 2 diabetes, cardiovascular diseases, and mortality.

Tesamorelin is a synthetic analog of human growth hormone-releasing factor, also known as growth hormone-releasing hormone (GHRH), which is indicated for the treatment of excess abdominal fat in HIV-infected patients with lipodystrophy.

The objectives of our paper were to

1) evaluate the utility of patient characteristics and validated disease-risk scores, including indicator variables for the metabolic syndrome and the Framingham Risk Score (FRS), as predictors of  visceral adipose tissue reduction during tesamorelin therapy, and

2) to explore the characteristics of patients who reached a threshold of VAT <140 cm2, a level associated with lower risk of adverse health outcomes, after 6 months of treatment with tesamorelin.

The basis of the report was a pooled analysis of the two pivotal, randomized Phase 3 trials of tesamorelin in 806 HIV-infected patients with excess abdominal fat. Our results indicate that presence of metabolic syndrome, high triglycerides, and white race are associated with a greater likelihood of responding to 6 months of tesamorelin treatment. The most robust response appears to be in subjects with VAT above 140 cm2, as well as those in the overweight range for body mass index (BMI) measures.

Continue reading

Brown Fat Transplants May One Day Cure Type I Diabetes

Subhadra Gunawardana DVM, Ph.D Research Associate Professor Department of Molecular Physiology & Biophysics Vanderbilt University Medical Center Nashville, TN 37232MedicalResearch.com Interview with:
Subhadra Gunawardana DVM, Ph.D

Research Associate Professor
Department of Molecular Physiology & Biophysics
Vanderbilt University Medical Center
Nashville, TN 37232

Medical Research: What is the background for this study? What are the main findings?

Response: For many years the general consensus has been that insulin replacement is essential for treating type 1 diabetes. Recent studies increasingly show that extra-pancreatic hormones, particularly those arising from adipose tissue, can compensate for insulin, or entirely replace the function of insulin under appropriate circumstances. Our work on mouse models show that type 1 diabetes can be effectively reversed without insulin, through subcutaneous transplantation of embryonic brown adipose tissue (BAT). BAT transplantation leads to replenishment of recipients’ white adipose tissue; dramatic decrease of inflammation; secretion of a number of beneficial adipokines; and fast and long-lasting euglycemia. Insulin-independent glucose homeostasis is established physiologically, through a combination of endogenously generated hormones arising from the transplant and/or newly-replenished white adipose tissue.

Medical Research: What should clinicians and patients take away from your report?

Response: If translated to human patients, this approach could provide a cure for type 1 diabetes that does not require regular exogenous administration of insulin or any other compound, and would thus avoid the many inherent difficulties with such therapies.

Continue reading

Recommendations To Restrict Dietary Fat Not Supported By Clinical Trials

James J. DiNicolantonio, PharmD Associate Editor BMJ Open Heart Cardiovascular Research Scientist Saint Luke's Mid America Heart InstituteMedicalResearch.com Interview with:
James J. DiNicolantonio, PharmD
Associate Editor BMJ Open Heart
Cardiovascular Research Scientist
Saint Luke’s Mid America Heart Institute

 

Medical Research: What is the background for this study? What are the main findings

Response: There were 6 randomized controlled dietary trials performed before the government dietary fat recommendations were released.  When we performed a systematic review and meta-analysis of the available trials at this time, there was no significant difference in all-cause mortality or cardiovascular heart disease mortality.  In essence, there was no support from randomized controlled trials at the time to support a reduction in fat and saturated fat (and there still isn’t from recent meta-analysis including newer trials).

The reductions in mean serum cholesterol levels were significantly higher in the intervention groups but this did not result in significant differences in cardiovascular heart disease or all-cause mortality. Continue reading

Discovering A Protein That Blocks Cells From Becoming Fat Cells

Dr. Richard Phipps PhD Department of Environmental Medicine and Flaum Eye Institute, School of Medicine and Dentistry, University of Rochester, Rochester, New YorkMedicalResearch.com Interview with:
Dr. Richard Phipps PhD
Department of Environmental Medicine and Flaum Eye Institute,
School of Medicine and Dentistry, University of Rochester, Rochester, New York

Medical Research: What is the background for this study? What are the main findings?

Response: Obesity has risen dramatically over the past 30 years in the United States and throughout the world. Obesity increases morbidity and mortality by increasing health problems such as Type 2 diabetes, cardiovascular disease and cancer. Thus, obesity is one of our greatest challenges worldwide. Our laboratory has been studying a protein called Thy-1 for several decades. Until now its’ true function was unknown. The main finding from our research is that when cells express this protein on their surface, they are inhibited from becoming fat cells. We show in a mouse model system that mice, which lack Thy-1, and given a high fat diet, increase weight much faster than mice that express Thy-1. These mice that lack Thy-1, also have increased levels of many proinflammatory mediators in their blood. In human cells, those that express high levels of Thy-1 are blocked in their ability to become fat cells, unlike the human cells from different tissues that do not express Thy-1. Thus, the main finding is that learning how to manipulate Thy-1 expression could lead to reduced fat cells and reduced fat production. Not only is this an important finding for obesity, but there are many human diseases that are caused by excess fat production in organs, such as, the orbit of the eye, the liver, and the bone marrow.

Continue reading

Snacking Between Meals May Increase Liver and Belly Fat

Mireille Serlie, MD PhD Academic Medical Center University of Amsterdam Department of Endocrinology and Metabolism Amsterdam, The NetherlandsMedicalResearch.com Interview with:
Mireille Serlie, MD PhD
Academic Medical Center
University of Amsterdam
Department of Endocrinology and Metabolism
Amsterdam, The Netherlands

MedicalResearch What are the main findings of the study?

Dr. Serlie: We studied the effects of hypercaloric high sugar or high fat/high sugar drinks consumed with the 3 main meals (representing an increase in meal size) or in between the 3 main meals (representing an increase in meal frequency or snacking). All subjects gained a similar amount of body weight but only the ones that snacked showed an increase in liver and abdominal fat. This suggests that besides caloric content and diet composition, eating pattern independently contributes to liver and abdominal fat accumulation. We also observed a trend for a decrease in hepatic insulin sensitivity in the high fat/high sugar frequency group only.

Continue reading

Fat and Hair Growth Synchronized By Same Signalling Pathway

Professor Rodney Sinclair University of Melbourne and Epworth Hospital Melbourne, VIC, AustraliaMedicalResearch.com Interview with:
Professor Rodney Sinclair
University of Melbourne and Epworth Hospital
Melbourne, VIC, Australia

 

MedicalResearch.com: What are the main findings of the study?

Answer: Activation of Wnt signalling promoted hair growth and fat growth.  Inhibition of Wnt signalling reduces fat growth and hair growth.  We looked at the fat layer on the scalp.  It was reduced by 50% over the bald areas of alopecia areata.  The patch of alopecia areata we looked at was new- only appeared a few days earlier and so the changes in fat thickness are rapid.

What is interesting is that the fat layer is dynamic, and significant fluctuations can occur in a rapid period of time in sync with the hair cycle.  It is also interesting that ligands for BMP6 and IGF2 are pro-adipogenic.

There are a couple of bigger questions that earlier media reports did not focus on- namely upstream factors regulating the hair cycle clock and the beauty of synchronization of fat and hair growth for seasonal thermal insulation.

Continue reading

Emergence of New Fat Cells and Response to Diet and Cold

Philipp E. Scherer, PhD Professor, Department of Internal Medicine Gifford O. Touchstone Jr. and Randolph G. Touchstone Distinguished Chair in Diabetes Research Director, Touchstone Diabetes Center The University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-8549MedicalResearch.com Interview with:
Philipp E. Scherer, PhD
Professor, Department of Internal Medicine
Director, Touchstone Diabetes Center
The University of Texas Southwestern Medical Center
Dallas, TX 75390-8549

MedicalResearch.com: What are the main findings of the study?

Dr. Scherer: This is the first study that tracks the emergence of new fat cells in response to various physiological stimuli, such as high fat diet and cold exposure.  Continue reading