Research in Diseases, Disorders, and Health Conditions
Chronic Diseases and Organ Systems
Obesity148 is a major contributor to serious health conditions in children and adults. Individuals who are obese have increased risk for type 2 diabetes, heart disease, stroke, many forms of cancer, osteoarthritis, liver disease, gallbladder disease, urinary incontinence, sleep disordered breathing, dementia, and many other diseases and conditions. Defined as an excess of body fat, obesity develops when the number of calories consumed in food and beverages exceeds the number of calories that the body burns to fuel basic life functions, physical activity, and normal growth during childhood. A complex interplay of factors influences obesity, from genetics and other aspects of our biology to chemical exposures and a range of other environmental factors to psychological and behavioral factors.
Given the alarming rate of increase in obesity, NIH invests significantly in a broad portfolio of basic, clinical, and translational research to: 1) understand the complex factors that regulate body weight and that contribute to obesity, 2) test obesity prevention and treatment strategies for children and adults, and 3) build the evidence base to inform local and national policies. Many studies include racially/ethnically-diverse and socioeconomically-disadvantaged populations and populations in geographic areas burdened by obesity.
Basic research in obesity looks at numerous risk factors that may predispose an individual towards obesity. Factors currently under investigation include genetic contributions; the role of gut microbes and how these microbes may be affected by different diets; circadian desynchronizations such as sleep deficiency; the role of different types of fat tissue, such as brown fat; developmental exposure to a variety of environmental chemicals, such as arsenic and bispenol A; sex differences, as related to sleep, reproductive health, sex hormones, pregnancy, etc.; psychosocial and behavioral factors such as the role of social settings on food consumption; and environmental factors such as research on the effect of policies on food choices and how nutritional information and costs of health and unhealthy foods affect purchasing patterns.
Findings in basic research indicate potential new approaches toward combatting this rising epidemic. For example, studies have shown that high maternal glucose during pregnancy correlates with obesity risk in children, suggesting a potential avenue for intervention. Scientists have also found that disruption of circadian rhythms can lead to fat accumulation in the liver, increasing vulnerability to diabetes, obesity, and other metabolic problems.
Translational research in obesity capitalizes on these advances to provide new directions in preventing and treating obesity. For example, scientists have discovered a way to make white fat (common, subcutaneous fat) mimic the energy-burning properties of brown fat and muscle in rats.149 Depletion of the neurotransmitter Neuropeptide Y in the brain resulted in active brown fat development and reduced body weight in rats, as well as protection from insulin resistance normally associated with a high fat diet.150 In another study, researchers demonstrated that blockade of a specific receptor of endocannabinoids (chemicals that affect many processes, such as pain, memory, apetite, etc.) can lead to weight loss and reduced cardiovascular and metabolic risks in obese mice as well as in overweight or obese humans. However, this blockade may also result in negative psychiatric side effects due to blockade of these receptors in the brain. A novel receptor inhibitor that does not cross the blood-brain barrier was developed and tested in a mouse model of obesity, resulting in weight loss and other beneficial metabolic changes. Results suggest this class of receptor inhibitors may be effective for treatment of fatty liver disease due to obesity or heavy alcohol use.151
NIH invests significantly in clinical and postclinical research to address current obesity. Several of the intervention strategies being investigated focus on behavioral and environmental changes to foster healthier eating and physical activity, based in a variety of contexts, such as the home, schools, healthcare, and other community settings. Other strategies under study include medical or surgical interventions.
NIH-funded researchers are examining the benefits of lifestyle interventions for adults delivered in a variety of places, including community settings such as the YMCA, primary care clinics, faith-based sites, the workplace, and the internet. Study populations are drawn from urban and rural areas, may encompass state-wide populations, are sometimes gender specific, and include diverse race/ethnic groups.
Such studies are showing significant benefits. For example, researchers funded through NHBLI’s Practice-Based Opportunity for Promotion of Weight Reduction program demonstrated that obese adults who received weight loss coaching via phone, online, and email contact, as well as support from their primary care providers, lost a significant amount of weight—5 percent or more of their starting body weight—and kept it off for two years.152In another study, lifestyle counseling sessions combined with the option to use weight loss medication or meal replacements, such as liquid shakes or meal bars, helped about one-third of obese participants lose a significant amount of weight and keep it off for two years.153
The long-term effects of bariatric surgery are being examined through NIDDK’s multi-center Longitudinal Assessment of Bariatric Surgery study. Scientists have recently found that gastric bypass surgery affects brain activation and reduces the desire to eat, particularly high-calorie foods.154
Many NIH ICs are investing in research to address the alarming rise of obesity in children and youth. Led by NCI with participation by many other ICs, The National Collaborative on Childhood Obesity Research (NCCOR) is a joint effort of NIH, CDC, USDA, and the Robert Wood Johnson Foundation, with the goal of improving the efficiency, effectiveness, and application of childhood obesity research through enhanced coordination and collaboration. In 2011, NCCOR launched new online resources for researchers: the Catalogue of Surveillance Systems, which includes surveillance systems relevant to childhood obesity research and the evaluation of policy and environmental interventions, and the Measures Registry, a database of measures related to diet and physical activity.
Several ongoing trials seek to prevent or treat childhood obesity. For example, NIDDK and other ICs funded a new set of studies of lifestyle interventions (“LIFE-Moms”) for overweight and obese pregnant women, designed to improve weight and metabolic outcomes for the women and their children. Four randomized trials are testing interventions to prevent excess weight gain in non-overweight youth and in those already overweight, and/or to reduce weight in obese and severely obese youth by targeting preschoolers, pre-adolescents, or adolescents. Other intervention strategies that focus on parents are also being explored, such as an intensive, family-based lifestyle intervention program for ethnically diverse children that was shown to result in sustained reductions in body weight and indicators of increased diabetes risk.155
A number of trials are addressing school-based interventions. For example, the NIDDK-supported HEALTHY study showed that an intervention in middle schools lowered the obesity rate in students at highest risk for type 2 diabetes (those who started out overweight or obese in sixth grade). However, schools that implemented the program did not differ from comparison schools in the overall prevalence of overweight/obesity.156
Researchers are examining community-level interventions. For example, the NHLBI-led Healthy Communities Study examines 275 communities and almost 24,000 children, ages 3–15, to identify characteristics of existing obesity-related community programs and policies that are associated with less childhood obesity and better eating and physical activity behaviors. NHLBI supports trials among American Indians and Alaska Natives to test community-responsive interventions to reduce childhood obesity and/or improve eating and activity behaviors in children.
For older children and young adults, the Early Adult Reduction of Weight through Lifestyle intervention study includes six trials, led by NHLBI and including NICHD, that are testing behavioral approaches for weight control in young adults 18–35 years of age at high risk for weight gain, including pregnant and postpartum women, community college or university students, and young adults trying to quit smoking. Interventions are delivered using technologies such as smart phones, social networking sites, Bluetooth-enabled scales, and text messages.
Finally, multiple efforts are underway to communicate evidence-based approaches towards preventing and treating obesity. NHLBI, in collaboration with NIDDK, is updating the Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: Expert Panel Report.157 The panel is using a rigorous evidence-based approach and innovative information technology to identify, review, and evaluate the scientific evidence for specific research questions. Public outreach efforts include We Can! (Ways to Enhance Children’s Activity and Nutrition), a national public education outreach program to promote a healthy weight among children through efforts to improve food choices, increase physical activity, and reduce screen time. We Can! is managed by NHLBI with collaboration from NIDDK, NICHD, and NCI.
NIH is collaborating with Home Box Office (HBO) on its Obesity Project, titled The Weight of the Nation, which was aired beginning in 2012. NIH staff has been providing scientific input to HBO on this project for several years. The CDC and Institute of Medicine (IOM) are also involved, with the IOM leading the coordination of the government partners. The multi-part documentary series will include four shows for adults, three shows for children (HBO family series), and supplemental films that will be posted on the HBO Web site. The project is funded with support from Kaiser Permanente and the Michael & Susan Dell Foundation.
NIH research on obesity is guided by the NIH Obesity Research Task Force. In 2011, the Task Force developed a new, updated Strategic Plan for NIH Obesity Research, with extensive external input, framed around the following overarching themes:
148 An adult is considered to be obese when their body mass index exceeds 30 kg/m2.
149 For more information, see https://www.nih.gov/news/health/jul2011/niddk-05.htm.
150 Chao PT, et al. Cell Metab. 2011;13(5):573–83. PMID: 21531339.
151 Tam J, et. al. J Clin Invest. 2010; 120(8):2953–66. PMID: 20664173.
152 Appel LJ, et al. N Engl J Med. 2011;365(21):1959–68. PMID: 22085317.
153 Wadden TA, et al. N Engl J Med. 2011;365(21):1969–79. PMID: 22082239.
154 Ochner CN, et al. Ann Surg. 2011;253(3):502–7. PMID: 21169809.
155 Savoye M, et al. Pediatrics. 2011;127(3):402–10. PMID: 21300674.
156 HEALTHY Study Group, et al. N Engl J Med. 2010; 363(5):443–53. PMID: 20581420
157 For more information, see https://www.nhlbi.nih.gov/guidelines/obesity/obesity2/index.htm.