Dr Stacey Lockyer[/caption]
Dr Stacey Lockyer BSc(hons) MSc PhD RNutr
Nutrition Scientist
British Nutrition Foundation
Imperial House 6th Floor
London
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This in depth review examines the potential health benefits of resistant starch, a form of starch that is not digested in the small intestine and is therefore considered a type of dietary fibre. Some forms of resistant starch occur naturally in foods such as bananas, potatoes, grains, and pulses, and some are produced or modified commercially and incorporated into food products as a functional ingredient.
There has been increasing research interest in resistant starch, with a large number of human studies published over the last 10 years looking at a variety of different health outcomes such as postprandial glycaemia, satiety and gut health. The review summarises reported effects and explores the potential mechanisms of action that underpin them.
There is consistent evidence that consumption of resistant starch in place of digestible carbohydrates can aid blood glucose control and this has resulted in an approved health claim in the European Union. There is also some evidence that resistant starch can support gut health and enhance satiety, though much more research is needed in these areas.
Dr. Edwina Yeung[/caption]
Edwina Yeung, Ph.D
Investigator, Division of Intramural Population Health Research
Eunice Kennedy Shriver National Institute of Child Health and Human Development
MedicalResearch.com: What is the background for this study?
Response: About 1 in 5 pregnant women in the United States is obese. Other studies have looked at mothers’ obesity in terms of children’s development, but no U.S. studies have looked at whether there might be a contribution from the father’s weight.
MedicalResearch.com: What are the main findings?
Response: One of the main findings of this study is that maternal obesity is associated with a delay in fine motor skill-- the ability to control movement of small muscles, such as those in the fingers and hands. Paternal obesity is associated with a delay in personal-social skills including the way the child interacts with others. Having both a mother and a father with severe obesity (BMI≥35) was associated with a delay in problem solving ability.
Dr. De-Kun Li,[/caption]
De-Kun Li, MD, PhD
Senior Research Scientist
Division of Research
Kaiser Foundation Research Institute
Kaiser Permanente
Oakland, CA 94612
MedicalResearch.com: What is the background for this study?
Response: The composition of gut microbia (microbiome) has emerged as a key contributor to human disease risk. The external influence on the composition of microbiome in early childhood, especially in infancy, has been linked to increased risk of childhood obesity. Several studies have examined use of antibiotics in infancy and reported an association between use of antibiotics and increased risk of childhood obesity. This has caused a great uncertainty among both pediatricians and parents regarding treatment of infant infections. However, the previous studies failed to separate the effect of underlying infections for which antibiotics were used from the effect of the antibiotics itself. The contribution of our study was to examine the effects of infections and antibiotic use separately.
Prof. Jamal Tazi[/caption]
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.
Dr. Igho Onakpoya[/caption]
Igho Onakpoya MD MSc
University of Oxford
Centre for Evidence-Based Medicine
Nuffield Department of Primary Care Health Sciences
Oxford UK
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Several medicines used to treat obesity have been withdrawn from the market over the last few years. However, the reasons for, and time trends about their withdrawals have not been systematically researched.
We identified 25 anti-obesity medicines withdrawn from the market over the last 50 years. 23 of these analogues of amphetamine or fenfluramine, i.e., neurotransmitters.
The reasons for withdrawal in the overwhelming majority of instances were cardiovascular or psychiatric adverse reactions, and drug abuse and dependence.
Dr. Alec Zhang[/caption]
Chengcheng (Alec) Zhang, Ph.D.
Associate Professor
Hortense L. and Morton H. Sanger Professorship in Oncology
Michael L. Rosenberg Scholar for Medical Research
Department of Physiology
UT Southwestern Medical Center
MedicalResearch.com: What is the background for this study?
Response: New therapeutic targets and approaches are needed to effectively treat leukemia. Acute myeloid leukemia (AML) is the most common form of adult acute leukemia whereas acute lymphoblastic leukemia (ALL) is the most common form of cancer in children; ALL also occurs in adults. Although treatment of pediatric ALL is highly effective, a sizeable number of patients are non-responders who succumb to this disease. The outcome of ALL in adults is significantly worse than for pediatric ALL. Additionally, some types of ALL have a much poorer prognosis than others.
Dietary restriction, including fasting, delays aging and has prolonged effects in a wide range of organisms and has been considered for cancer prevention. In certain types of solid tumor,_ENREF_1 dietary restriction regimens are able to promote T cell-mediated tumor cytotoxicity and enhance anticancer immunosurveillance, and coordinate with chemotherapy to promote the anti-cancer effects. However, the responsiveness of hematopoietic malignancies to dietary restriction, including fasting, remains unknown. Furthermore, whether dietary restriction alone can inhibit cancer development is not clear.
Dr. Audrey Chu[/caption]
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.
Dr. Richard Hodin[/caption]
Richard Hodin, MD
Gastrointestinal and Endocrine Surgery
Professor of Surgery, Harvard Medical School
Chief of Academic Affairs, Department of Surgery,
Massachusetts General Hospital
Boston, Mass 02114
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Sugar substitutes like Aspartame are widely used and supposed to make people lose weight and have less diabetes, heart disease, etc. However, a number of studies indicate that theses substitutes don’t work very well. The reasons for them not working have not been clear. Our study found that the most common sugar substitute (aspartame) blocks an enzyme in our gut called Intestinal Alkaline Phosphatase (IAP). By blocking IAP, Aspartame prevents the beneficial effects of IAP which normally works to prevent obesity, diabetes, and other aspects of the metabolic syndrome.
So, we now have an explanation for why Aspartame may make obesity and the metabolic syndrome worse, rather than better.
Dr. Somwail Rasla[/caption]
Somwail Rasla, MD
Internal Medicine Resident
Memorial Hospital of Rhode Island
Brown University
MedicalResearch.com: What is the background for this study?
Response: Weight cycling has been studied as a possible risk factors for all-cause mortality and was found to be insignificant in some studies and significant in other studies when adjusted to age and timing of when the weight cycling occurred. It was proposed that weight cycling may increase risk of chronic inflammation by which weight cycling was considered to be a risk factor for increased morbidity and all cause mortalities. Other studies have reported that frequent weight cycling was associated with shorter telomere length, which is a risk factor for several comorbidities including CHD. Earlier studies showed that weight cycling has an association with increase in size of adipocytes as well as fluctuation of serum cholesterol, triglycerides, glucose, insulin, and glucagon which may contribute to the increased incidence of diabetes. Alternatively, in the nurses’ health study , weight cycling was not predictive of cardiovascular or total mortality.
(l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum UT Southwestern[/caption]
Dan Rosenbaum, Ph.D.
Principal Investigator
Department of Biophysics
The University of Texas Southwestern Medical Center
Dallas, Texas
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This study focuses on the structure of the human CB1 cannabinoid receptor.
The CB1 protein is a membrane-embedded G protein-coupled receptor (GPCR) in the brain and peripheral tissues that responds to a variety of different compounds, including endogenous lipid messengers (‘endocannabinoids’), plant natural products (such as THC from the Cannabis sativa plant i.e. marijuana), and synthetic antagonists (such as the taranabant ligand used for this study). The CB1 receptor is involved in regulating neurotransmission in vertebrates, and is a potential therapeutic target for numerous conditions including obesity, pain, and epilepsy.
The main findings of this study entailed the solution of the high-resolution crystal structure of human CB1 receptor bound to the inhibitor taranabant. This structure revealed the precise shape of the inhibitor binding pocket, which is also responsible for binding THC and endocannabinoids. In addition to helping explain the mechanism of inhibitor and THC binding, our structure provides a framework for computational studies of binding to a large diversity of cannabinoid modulators of therapeutic importance.
Dr. Ken Fujioka[/caption]
Ken Fujioka M.D.
Director of the Center for Weight Management
Scripps Clinical Department of Endocrinology
La Jolla CA
MedicalResearch.com: What is the background for this study?
Response: Obesity is an odd disease that has many causes (overeating, underactivity, the patient being placed on a medication that drives up weight and a whole lot of other causes that result in a higher weight) so trying to find the right treatment, in this case a weight loss medication, for a particular patient is not an easy task. If there is a way to find out if you’ve picked the right medication (a weight loss of at least 5%) then this can help you decide whether you should keep the patient on the medication or stop the medication.
There are two huge benefits to this:
1. Is that you find your responders (patients) that will go on to lose weight and do well and 2. When you stop the medication in the non-responders you eliminate any potential adverse events from the weight loss medication.
Thus this study was designed to find out if early weight loss can predict who will go on to lose a significant amount of weight on Liraglutide.
And yes those who lose weight go on to lose weight.
Dr. Lee Kaplan[/caption]
Lee Kaplan, MD, PhD,
Director of the Obesity, Metabolism and Nutrition Institute Massachusetts General Hospital Weight Center and
ACTION study steering committee member
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Today, nearly 100 million people in the U.S. have obesity. Despite the fact that many healthcare providers and others recognize obesity as a disease that can have a significant impact on health, many people with obesity do not have access to effective care for this disorder. As a result, obesity remains substantially under-diagnosed, under-addressed and under-treated. Since multiple parties could have a role in overcoming this barrier to effective obesity care, we sought to determine and compare the perspectives and experience of three important groups – health care providers, employers, and people with obesity themselves – about obesity and its care.
As the first national study looking simultaneously at these complementary perspectives, ACTION sought to help answer several important questions:
Dr. Patrick M. O'Neil[/caption]
Patrick M. O'Neil, Ph.D.
Director, Weight Management Center
Professor, Department of Psychiatry and Behavioral Sciences
Medical University of South Carolina
Charleston, SC 29425
MedicalResearch.com: What is already known about the subject?
• Even modest weight loss (2-5%) from clinical interventions improves glycemic control in type 2 diabetes.
• Commercial weight loss programs, comparatively more affordable and accessible than clinic-based modalities, can produce weight losses in this range, although they typically do not offer diabetes-specific counseling.
• Data are sparse on such programs’ effects on glycemic control for adults with T2DM.
Dr Todd Hobbs[/caption]
Dr Todd Hobbs MD
Chief medical officer (CMO)
Novo Nordisk in North America
MedicalResearch.com: What is the background for this study?
Response: There is little data that describes weight loss and other outcomes separately in early weight loss responders and early weight loss non-responders. Early weight loss, whether through lifestyle or pharmacotherapy, can be a good predictor of long-term weight loss. Consequently, all recently-approved weight loss medication labels include ‘stopping rules’ for discontinuing medication if a threshold weight loss is not achieved by a specified milestone. Bottom line, it’s important patients don’t continue on a therapy that isn’t working for them. This makes this form of research important from a clinical standpoint but also in the larger obesity treatment paradigm - including payers and how pharmaceutical treatments are labeled.
Prof. Paul Aveyard[/caption]
Paul Aveyard PhD MRCP FRCGP FFPH
Professor of Behavioural Medicine
Nuffield Department of Primary Care Health Sciences
University of Oxford
Radcliffe Primary Care Building
Radcliffe Observatory Quarter
Oxford
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We know that opportunistic brief interventions by physicians can be effective, but there is no evidence that they are so for obesity. Physicians worry that broaching this topic will be offensive, time-consuming, and ineffective. We needed a randomised trial to assess whether physicians’ fears were justified, or in fact brief interventions could be as effective for patients who are overweight as they are for smoking or problem drinking and that’s what we did.
Dr. Susan L. McElroy[/caption]
Dr. Susan L. McElroy, M.D.
Professor of Psychiatry and Behavioral Neuroscience
Chief Research Officer
Lindner Center of HOPE
University of Cincinnati College of Medicine.
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: SPD489-346, designed as a multi-center, double-blind, placebo-controlled, dose-optimized, randomized-withdrawal study, is the first-ever longer-term pharmacologic study (38 weeks) to evaluate the maintenance of efficacy between Vyvanse and placebo in adults with moderate to severe binge eating disorder (B.E.D.).
Study SPD489-346 evaluated the longer-term maintenance of efficacy (38 weeks) between Vyvanse and placebo based on the primary endpoint of time to relapse during the randomized-withdrawal phase in adults aged 18 to 55 (N=267) with moderate to severe B.E.D. based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition – Text Revision (DSM-IV-TR®) criteria. In the study, relapse was defined as having two or more binge days per week for two consecutive weeks prior to any visit and an increase in Clinical Global Impressions-Severity (CGI-S) score of two or more points relative to the randomized-withdrawal baseline visit
Results from SPD489-346 indicated that Vyvanse (n=136) demonstrated significant maintenance of efficacy compared to placebo (n=131) based upon the primary endpoint of time to relapse. At the conclusion of the study, maintenance of efficacy for patients who had an initial response during the open-label phase, and then continued on Vyvanse during the randomized-withdrawal phase, was demonstrated with Vyvanse being superior over placebo as measured by time to relapse.
Safety and tolerability evaluations of Vyvanse included treatment-emergent adverse events (TEAEs) and vital signs. The safety profile for Vyvanse in this study was generally consistent with the known profile reported in previous studies in adult patients with moderate to severe B.E.D.
Vyvanse is indicated for the treatment of moderate to severe B.E.D. in adults. Vyvanse is not for weight loss. It is not known if Vyvanse is safe and effective for the treatment of obesity.
Vyvanse is a federally controlled substance (CII) because it can be abused or lead to dependence. Keep in a safe place to prevent misuse and abuse. Selling or sharing Vyvanse may harm others and is illegal.
Dr. Artemis P. Simopoulos[/caption]
Artemis P. Simopoulos, M.D. FACN
President, The Center for Genetics
Nutrition and Health
Washington, DC 20016
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: I have written extensively on the evolutionary aspects of diet, the diet of Crete prior to 1960 in which I pointed to the misinterpretation of the data of the Seven Countries Study by Keys et al. A major characteristic of these diets is a balanced omega-6/omega-3 ratio.
The recommendation to substitute saturated fats with omega-6 rich oils (sunflower, corn, soybean) increases inflammation and coronary heart disease. It has been shown in a number of studies that a high omega-6/omega-3 (20/1 instead of a balanced ratio) leads to an increase in white adipose tissue and prevents the formation of brown adipose tissue leading to obesity. The changes in the diet-high in omega-6 oils depletion of omega-3 and high fructose along with highly refined carbohydrates in processed foods and a sedentary lifestyle lead to obesity, diabetes, coronary heart disease and cancer.
The scientific evidence from the FAT-1 mouse and recent cohort studies clearly show that the current dietary guidelines as the previous ones are not based on science that takes into consideration genetics, metabolism, the concept that a calorie is not a calorie. It is important to consider that nutrients influence the expression of genes, the omega-6 fatty acids are the most pro-inflammatory nutrients, and inflammation is at the base of all chronic non-communicable diseases.
Dr. Annette Schürmann[/caption]
Annette Schürmann PhD
Department of Experimental Diabetology
German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)
Nuthetal
Germany German Center for Diabetes Research (DZD
München-Neuherberg Germany
MedicalResearch.com: What is the background for this study?
Response: The aim of our study was to clarify why genetically identical mice respond very different to a high fat diet. Some of the mice react with an elevated body weight, others not. We analyzed the expression pattern
of liver at two time points, at the age of 6 weeks, (the earlierst time
point to distiguish between those that respond to the diet (responder
mice) and those that did not (non-responders)), and at the age of 20
weeks. One transcript that was significantly reduced in the liver of
responder mice at both time points was Igfbp2. The reason for the
reduced expression was an elevated DNA-methylation at a position that is
conserved in the mouse and human sequence. The elevated DNA-methylation
of this specifc site in human was recently described to associate with
elevated fat storage (hepatosteatosis) and NASH. However, as 6 weeks old
mice did not show differences in liver fat content between responder and
non-responder mice we conclude that the alteration of Igfbp2 expression
and DNA metyhlation occurs before the development of fatty liver.
Our data furthermore showed that the epigenetic inhibition of Igfbp2
expression was associated with elevated blood glucose and insulin
resistance but not with fatty liver.
Dr. Li-Jun Yang[/caption]
Li-Jun Yang MD
Professor, Hematopathology
University of Florida
MedicalResearch.com: What is the background for this study?
Response: Irisin, an exercise-induced myokine, promotes converting subcutaneous (sc) fat-storing adipocytes into fat-burning adipocytes, namely “browning”. Although beneficial effects of irisin such as browning and weight loss in obese animal have been observed in mice, the effect of irisin in human adipocytes is controversial. Moreover, the mechanisms of irisin’s anti-obesity are not clear and systemic studies are not available using human adipose tissues. In our study, we aimed at exploring at the multiple levels in the mechanisms of irisin’s anti-obesity effects using human adipocytes and human adipose tissues.
Dr. Ursula H. Winzer-Serhan[/caption]
Ursala. H. Winzer-Serhan Ph.D.
Associate Professor
Department of Neuroscience and Experimental Therapeutics
Texas A&M Health Science Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Nicotine is a plant alkaloid that is naturally occurring in the tobacco plant. Smoking delivers nicotine to the brain where it acts as a stimulant. Tobacco and electronic cigarette smoking delivers many other chemicals to the body, which are harmful and can cause cancer.
However, the drug nicotine by itself is relatively benign and poses few health risks for most people. Nicotine acts in the brain on nicotinic receptors, which are ion channels that are widely expressed in the brain. They play an important role in cognitive functions. Research with rodents and in humans has shown that nicotine can enhance learning and memory, and furthermore, can protect neurons during injuries and in the aging brain. With the increasingly older population, it becomes more and more important to delay cognitive decline in the elderly. Right now, there is no drug available that could delay aging of the brain.
Dr. Makoto Fukuda[/caption]
Makoto Fukuda Ph.D.
Assistant Professor
Children's Nutrition Research Center
Department of Pediatrics
Baylor College of Medicine
Houston, Texas 77030
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: A hallmark characteristic of obesity is diminished actions of metabolic hormones that are critically required to maintain whole body energy balance and glucose homeostasis. Leptin is a crucial and powerful hormone that keeps body weight normal. It was hoped that leptin might be a “magic bullet” that could cure obesity. Shortly after the discovery, however, obese individuals were found to have little or no response to exogenously administered leptin, a state of “leptin resistance”. These observations created a central question to be addressed in the field, which would help our understanding of the core of pathophysiology of obesity. While we and other groups previously demonstrated that Epac, a signaling molecule known as a GTP/GDP exchange factor directly activated by cAMP, is involved in cellular leptin resistance, the role of brain Epac signaling in the whole body metabolism has not yet established.
We approached this question by using brain-specific knockout mice of Rap1, a direct activator of Epac. As expected from previous results, mice with brain-specific deficiency of Rap1 failed to develop leptin resistance even when they were challenged with a hypercaloric diet. What impressed us most in this study was that Rap1 in the brain plays a key role in the whole body metabolic control, beyond its role in controlling leptin sensitivity. Loss of brain Rap1 protects mice from diet-induced obesity and disordered glucose balance, whereas these knockout mice maintained a similar body weight to that of control mice on a normal regular diet. Further, pharmacological inhibition of this pathway reversed leptin resistance and reduced the body weight of dietary obese mice. At the cellular level, we found an unexpected link between Rap1 and endoplasmic reticulum (ER) stress that has emerged as a causative contributor to the development of leptin resistance.