RESEARCH

Research in the Department of Nutrition Sciences is designed to probe the mechanisms behind chronic metabolic disease (diabetes, cancer, cardiovascular disease, etc.), particularly as they relate to obesity, diabetes, and nutrition.

Our investigators use state-of-the-art techniques for assessing body composition, energy metabolism, and metabolic health in humans and animal models. We also study how lifestyle changes (e.g., diet, exercise, weight loss) impact health. We have two NIH Center Grants (Nutrition Obesity Research Center, Diabetes Research Center) in our department. Our faculty have published more than 165 publications over the past two years and are PIs on 60 grants.

Food As Medicine

BARBARA GOWER, PHD

Professor, Vice Chair for Research

Drs. Barbara Gower and Amy Goss have an active research program that has shown that “what” you eat matters. Rather than focusing on calories and weight loss, the investigators look at diet composition and how it affects risk factors for metabolic diseases such as type 2 diabetes. The investigators found that, even without weight loss, lowering the amount of carbohydrate in the diet can “remodel” the body. Specifically, “bad” fat such as visceral fat and liver fat disappears, while “good fat” (thigh fat) remains. A recent study in children with fatty liver disease showed that when the children reduced their carbohydrate intake to ~100 g per day, liver fat declined. This study AMY GOSS, PHD, RD

Assistant Professor

was “family based,” meaning that the whole family changed their eating habits to match those of the children. The children randomized to the lower carb diet also lost more weight than those consuming a “USDA”-type (food pyramid, or “my-plate”) diet. Dr. Goss will soon be conducting a follow-up study in the same population to look at how changes in liver fat affect hepatic insulin sensitivity and risk for type 2 diabetes. On the other end of the age spectrum, Drs. Gower and Goss also recently completed a study in older adults (>65) with obesity. Even without intentionally restricting food intake, those adults randomized to the lower carb diet consumed fewer calories and lost weight. They also lost harmful visceral fat and intermuscular fat. Ongoing NIHfunded research is testing the hypothesis that a weight-maintaining diet with few carbs will help patients with type 2 diabetes gain disease remission by depleting pancreatic lipid and restoring beta-cell function. A second NIH-funded study is determining if “matching” diet composition to metabolic phenotype (insulin sensitivity and insulin secretion) is helpful for both weight loss and weight loss maintenance in African-American women with obesity. ■

Goss AM, Gower B, Soleymani T. et al. Effects of weight loss during a very low carbohydrate diet on specific adipose tissue depots and insulin sensitivity in older adults with obesity: a randomized clinical trial. Nutr Metab (Lond) 17, 64 (2020). https://doi.org/10.1186/s12986-020-00481-9 Goss AM, Dowla S, Pendergrass M, Ashraf A, Bolding M, Morrison S, Amersam A, Soleymani T, Gower BA. Effects of a carbohydraterestricted diet on hepatic lipid content in adolescents with non-alcoholic fatty liver disease: a pilot, randomized trial. Pediatric Obesity. 2020. Jul;15(7):e12630. doi: 10.1111/ijpo.12630. Epub 2020 Mar 4. PMID: 32128995.

DREW SAYER, PHD Assistant Professor

Drs. Drew Sayer, Holly Wyatt, and James Hill are also testing the hypothesis that “what” you eat matters. However, in this case, they are testing whether red meat is any different from other protein sources when consumed by individuals with type 2 diabetes. This study responds to the comments frequently seen in the popular press regarding the association between red meat and diseases outcomes. Based on epidemiological (observational) data, there is a perception that red meat consumption is associated with adverse health outcomes. However, observational studies can be confounded, leading to incorrect conclusions. HOLLY WYATT, MD

Professor, Vice Chair for Clinical Programs

Red meat is an excellent source of dietary protein, which is critical for maintaining a healthy body composition. High-quality protein is particularly important during weight loss, where it can help maintain muscle mass as fat mass is lost. Prospective, carefully controlled studies examining the effect of red meat consumption on body composition and metabolic health are lacking. The Sayer-Hill study, funded by the Beef Checkoff, will determine whether a healthful weight loss protocol is more or less effective in maintaining muscle mass with weight loss and controlling blood glucose if it includes regular consumption of beef. ■

Timing Is Everything

COURTNEY PETERSON, PHD

Associate Professor

In addition to “what” you eat, “when” you eat might also affect health outcomes. Some studies have shown that eating earlier in the day is associated with greater weight loss, even when total energy intake isn’t emphasized. Dr. Courtney Peterson is interested in figuring out why eating earlier in the day might make it easier to lose weight. Is it because people eat less? Or does their metabolism change? These questions are the topic of Dr. Peterson’s ongoing research funded by the NIH and DOD. Dr. Peterson has already completed one study on this topic that looked at metabolic factors. She discovered that blood glucose levels were lower in people who ate earlier in the day (rather than later in the day), even when calories were matched. She recently received funding from the Department of Defense and the NIH to pursue this line of research. The DOD study is designed specifically to determine whether eating earlier in the day will lead to better glucose control in a population with type 2 diabetes that includes veterans. In this study, Dr. Peterson also will determine whether light therapy, which alters or aligns circadian rhythms, affects glucose control. The NIH study will also look at how meal timing affects metabolic health in individuals with prediabetes, examining three eating “windows”: 8 a.m.–2 p.m., 2 p.m.–8 p.m., and 8 a.m.–8 p.m. The primary endpoint is 24-h glycemic control. ■

Jamshed H, Beyl RA, Della Manna DL, Yang ES, Ravussin E, Peterson CM. Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans. Nutrients. 2019 Jun;11(6):1234.

Cancer: More Than Just Bad Genes

LYSE NORIAN, PHD

Associate Professor

DANIEL SMITH JR, PHD

Assistant Professor

Although most people think about type 2 diabetes and heart disease as obesity-related diseases, cancer is also a metabolic disease that responds to diet and nutrition. Drs. Lyse Norian and Daniel Smith are working with animal models to understand how diet composition affects cancer outcomes. They are blocking the ability of the body to use dietary starch and seeing if this “low starch” diet improves the effectiveness of cancer treatments. The “starch blocker” is called “acarbose,” and it is currently available as a treatment for type 2 diabetes, where it helps lower blood sugar. The NorianSmith study will determine if acarbose can also be used to improve outcomes in cancer patients. Their study is looking specifically at whether cancer drugs that act through the immune system are more effective in combating cancer when blood glucose is lowered by acarbose. ■

JT Gibson, RM Orlandella, WJ Turbitt, M Behring, U Manne, RE Sorge, and LA Norian. “Obesity-associated myeloid-derived suppressor cells promote apoptosis of tumor infiltrating CD8 T cells and immunotherapy resistance in breast cancer.” 2020. Frontiers in Immunology. Frontiers in Immunology. Oct.6,11:590794. doi: 10.3389/fimmu.2020.590794. PMID: 33123173. RM Orlandella, WJ Turbitt, JT Gibson, SK Boi, P Li, DL Smith, Jr., LA Norian. “The antidiabetic acarbose impedes tumor progression and improves the efficacy of both anti-PD-1 and mTOR inhibition in pre-clinical renal cancer.” 2020. Cancers (Basel). Oct 6;12(10):2872. doi: 10.3390/ cancers12102872.PMID: 33036247.

WENDY DEMARK-WAHNEFRIED, PHD, RD

Professor, Webb Endowed Chair

Dr. Wendy Demark-Wahnefried’s “Harvest for Health” study showed that vegetable gardening led to a decrease in waist girth and a slowing of the aging process. In addition, her web-based diet and exercise intervention is now being provided to 652 cancer survivors in Alabama, Mississippi, North Carolina, and Tennessee. Dr. Demark-Wahnefried is using a novel method for assessing muscle mass in cancer survivors that can be done remotely with a simple urine test. Cancer causes muscle wasting, and methods for preventing and tracking changes in muscle are needed. The method involves tracking the muscle metabolite creatine through the use of stable isotopes. These studies are likely to revolutionize how we deliver and assess lifestyle interventions and make them available to cancer survivors, as well as others more broadly. ■

Demark-Wahnefried W, Rogers LQ, Gibson JT, Harada S, Frugé AD, Oster RA, Grizzle WE, Norian LA, Yang ES, Della Manna D, Jones LW, Azrad M, Krontiras H. Randomized trial of weight loss in primary breast cancer: Impact on body composition, circulating biomarkers and tumor characteristics. Int J Cancer. 2019 Aug 23. 2020;146: 2784–96 PMID:31442303.

A New International Registry to Study Obesity

Drs. James Hill, Drew Sayer, and Holly Wyatt have helped create the International Weight Control Registry to study obesity. This project involves multiple research groups throughout the world who are combining efforts to collect data from a newly established online cohort of individuals who have attempted weight loss either successfully or unsuccessfully. The hope is to learn from these participants to be better able to produce and maintain weight loss. The Nutrition Obesity Research Center received an NIH grant to accelerate this study.

Prenatal Programming

Genes and Aging

W. TIMOTHY GARVEY, MD

Professor, Director, Diabetes Research Center

Although nutrition interventions in patients with obesity and disease are critical, prevention is ultimately the key to health. And it’s never too early to start. Increasing evidence suggests that maternal health affects the developing fetus in ways that cause lasting metabolic effects; a kind of “programming” that occurs in utero. Most of the studies that document these effects have been done in animal models. In a ground-breaking attempt to translate this line of research to humans, Drs. W. Timothy Garvey and Paula Chandler-Laney wrote and received a large grant from the American Heart Association to study the mechanisms through which obesity and diabetes “program” the fetus during pregnancy. The project involves both basic science (rodent) studies and clinical studies. The underlying hypothesis is that epigenetic modifications take place in utero that have a lasting effect on the metabolism of the offspring, ultimately affecting risk for chronic disease. “Epigenetic” changes are modifications to the DNA (genetic material) that affect how genes are transcribed. They are thought to be one of the means through which environmental variables can influence development. In the AHA study, the investigators are looking at maternalPAULA CHANDLER-LANEY, PHD

Associate Professor

offspring dyads in early childhood (4–10 years) to determine whether the weight status and metabolic health of the child reflect maternal weight and diabetes status during pregnancy. Children will be assessed for body fat mass, insulin resistance, leptin resistance, inflammation, energy balance, and substrate oxidation to identify contributors to obesity. Epigenetic differences associated with obesity-related phenotypes in the high-risk groups (i.e., maternal obesity, with and without diabetes) as compared to the low-risk group (maternal normal weight and no diabetes) will be identified in the 4–10-year-old children and then used to inform a more targeted inspection of relevant genes in the second and third projects. The second project is recruiting a parallel group of pregnant women to prospectively look at the association of weight and diabetes status in pregnancy of offspring outcomes during the first three months of life, and in the third aim, rodent models are used to mimic the human prenatal conditions. Ultimately, investigators hope that information from this study will provide mechanistic insights about how obesity propagates across generations. ■

MARIA DE LUCA, PHD

Associate Professor

Genetic variation also may affect how individuals age. Dr. Maria De Luca studies the syndecan gene, which is involved in the structure of the body’s tissues. Mutations in this gene are associated with increased body fat, which may contribute to obesity. Mutations are also associated with hypertension, coronary artery disease, and triglyceride levels. Dr. De Luca believes that deficiency of syndecan activity in fat tissue promotes the break down of cells as a protective mechanism. This “protective” strategy is beneficial in the short-term but can lead to tissue dysfunction and accelerated aging in adults. Dr. De Luca was recently funded by NIH to test this hypothesis in mice, where the gene can be manipulated. ■