Location: Dietary Prevention of Obesity-related Disease Research
2024 Annual Report
Accomplishments
1. Time-restricted feeding restores daily metabolic rhythm in adult obese mice. Obesity in adults presents a great challenge in clinical practice for improving metabolic health and reducing the mortality of obesity-related diseases. Erratic eating behavior disturbs daily metabolic rhythm and leads to excess body fat. Time-restricted feeding is a dietary practice where food intake is restricted to a fixed time of the day (for example, daytime for humans) that establishes a consistent daily eating pattern and prevents erratic eating behavior. Using a model for adult obesity, ARS scientists in Grand Forks, North Dakota, found that time-restricted feeding does not affect body fat mass but restores daily metabolic rhythm, improves insulin sensitivity, and decreases cholesterol in adult obese mice. Over 40% of U.S. adults are obese (108.5 million). Reduction of body weight in adults with obesity is considered a standard of treatments in clinical practice. However, initial and sustained weight loss remains a great challenge because of the multiple behavior changes required for effective weight control. This research informs clinical practice by demonstrating the benefits of the healthy eating behavior on a regular, fixed-time basis for improving metabolic health. This research is of an interest to health care providers, scientists in government and academia, and the general public.
2. Identification of a pro-inflammatory gene which causes intestinal inflammation in a diet-induced obese mouse model. Consumption of a high-fat diet is associated with obesity and colonic inflammation. However, the causality between diet and obesity-related colonic inflammation/cancer remains to be determined. ARS scientists in Grand Forks, North Dakota, demonstrated that the knockout of tumor necrosis factor (TNF) alpha gene reduces intestinal tumorigenesis in obese mouse models. This research provides novel mechanistic insights into the diet-related obesity and colon cancer at gene levels. These findings would be instrumental in adopting precision nutrition strategies tailored to preventing obesity-related diseases. This work is of interest to health professionals, basic and clinical scientists, and the general public.
3. Fermentation products of dietary fiber (in the colon) inhibit colon cancer cell proliferation. Increasing dietary fiber consumption is linked to lower colon cancer incidence, and this anticancer effect is tied to elevated levels of short-chain fatty acids (e.g., butyrate) because of the fermentation of fiber by colonic bacteria. ARS scientists at Grand Forks, North Dakota, demonstrated that butyrate effectively inhibits colon cancer cell proliferation, which is a gene-directed and cell type specific-dependent process. These mechanistic data (in human cultured colon cell models) may help explain clinical variability of butyrate’s benefits. This research is of interest to health care providers, scientists in government and academia, and the general public.
4. Inadequate calcium intake decreases bone mass without affecting fat mass in estrogen-deficient rat model. Obesity induced by a high-fat diet is detrimental to bone structure. Studies show calcium intake affects bone mass and fat mas. Whether calcium deficiency affects bone in obese rats with estrogen deficiency is unknown. ARS scientists at Grand Forks, North Dakota, demonstrated that inadequate calcium intake and a high-fat diet have independent negative effects on bone structure and calcium deficiency does not affect fat mass. The findings are of interest to researchers in basic and clinical areas, as well as the general public as the study suggests that adequate calcium intake and/or reducing obesity benefits bone health.
5. Incorporation of dry edible beans to a high-fat diet does not affect body composition and bone structure in obese mice. Studies have demonstrated health benefits of pulse consumption in humans, including reduction in obesity-induced chronic disorders. The 2020 USDA Dietary Guidelines for Americans recommend weekly intake up to 1.5 cups of dry edible beans (pulses) as part of healthy U.S.-style dietary pattern. ARS scientists at Grand Forks, North Dakota, demonstrated that including pulses in a high-fat diet increases certain mineral content in bone but has minimal beneficial effect on lean body mass and bone structure in obese mice. The findings are of interest to researchers in basic and clinical areas, as well as the general public as the study suggests that reducing obesity is important to improve bone mass.
Review Publications
Gregoire, B.R., Cao, J.J. 2023. Time of day of exercise does not affect the beneficial effect of exercise on bone structure in older female rats. Frontiers in Physiology. 14:1-11. https://doi.org/10.3389/fphys.2023.1142057.
Cao, J.J., Gregoire, B.R. 2024. Calcium deficiency decreases bone mass without affecting adiposity in ovariectomized rats fed a high-fat diet. Nutrients. 16(4). Article 478. https://doi.org/10.3390/nu16040478.
Yan, L., Rust, B., Palmer, D. 2024. Time-restricted feeding restores metabolic flexibility in adult mice with excess adiposity. Frontiers in Nutrition. 11:1-14. https://doi.org/10.3389/fnut.2024.1340735.
Oncel, S., Safratowich, B.D., Lindlauf, J., Liu, Z., Palmer, D., Briske Anderson, M.J., Zeng, H. 2024. Efficacy of butyrate to inhibit colonic cancer cell growth is cell type-specific and apoptosis-dependent. Nutrients. 16(4). Article 529. https://doi.org/10.3390/nu16040529.
Li, J., Tang, Y., Lin, T., Zeng, H., Mason, J.B., Lui, Z. 2023. Tumor necrosis factor-a knockout mitigates intestinal inflammation and tumorigenesis in obese Apc1638N mice. Journal of Nutritional Biochemistry. 117. Article 109355. https://doi.org/10.1016/j.jnutbio.2023.109355.
Peng, Y., Langermann, S., Kothari, P., Liu, L., Zhao, W., Hu, Y., Chen, Z., Li, J., Cao, J.J., Guo, X., Chen, L., Bauman, W.A., Qin, W. 2023. Anti-siglec-15 antibody prevents the marked bone loss after acute spinal cord injury-induced immobilization in rats. Journal of Bone and Mineral Research Plus. 7(12). Article e10825.