Nutrition Frontiers - Summer 2020

RESEARCH UPDATE: ON THE CLINICAL FRONT

Zinc Induces Potential Chemopreventive Activity in Barrett’s Esophagus

Zinc’s chemopreventive activity for esophageal cancer has been well demonstrated in animal models. In humans, zinc deficiency is associated with promotion of esophageal cancer. To determine if the chemopreventive action of zinc in animal models could extend to humans with Barrett’s esophagus (BE), Valenzano and colleagues placed patients with a prior BE diagnosis on oral zinc gluconate (26.4 mg, BID, for 14 days) or a placebo. Esophageal mucosal biopsies from the Barrett’s region found zinc-induced mRNA changes for a large number of transcripts, including downregulation of transcripts encoding proinflammatory proteins, upregulation of anti-inflammatory mediators, downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT), and upregulation of transcripts that oppose EMT. microRNA arrays showed significant upregulation of seven microRNAs with tumor suppressor activity. Although a cancer chemopreventive action by zinc in BE may be possible, prospective clinical trials could determine with certainty if zinc could prevent the growth of esophageal cancer in humans.  

RESEARCH UPDATE: WHAT’S NEW IN BASIC SCIENCE

Nutritional Environment Determines Intestinal Stem Cells Contribution to Colorectal Cancer

The high incidence of sporadic colorectal cancer (CRC) in Western societies is linked to long-term dietary patterns. Different stem cell populations play a role in mucosal homeostasis and initiating CRC tumors. In a unique mouse model for sporadic CRC, Li and colleagues weaned wild-type mice to: a purified rodent Western-style diet (NWD1) with lower levels of vitamin D₃, calcium, methyl donors, fiber and higher fat; a control diet, AIN76A; or the NWD2 diet (NWD1 + increased vitamin D and calcium). Feeding NWD1 rather than control diets redefined the contribution of two different stem cell populations to both mucosal homeostasis and tumorigenesis. The contribution of Lgr5^hi cells, a marker of intestinal stem cells, was reduced, whereas cells derived from the Bmi1+ compartment were substantially increased. Likewise, DNA mismatch repair (MMR), a key pathway in sporadic CRC, was reversed in Lgr5^hi cells isolated from mice fed NWD2 indicating MMR-upregulation is vitamin D/calcium dependent. This research highlights the potential impact of variable human diets on which and how stem cell populations function in the human mucosa and become tumorigenic.

Astrocyte Regulation of Glucose Metabolism and Reproduction by Sirtuin 1

Sirtuin 1 (Sirt1), an N

AD-dependent class III deacetylase, is activated during fasting or caloric restriction to increase fatty acid oxidation and gluconeogenesis and suppress insulin secretion, insulin action, and adipogenesis. In mice genetically modified to overexpress Sirt1 (OX) or express an inactive mutant form of Sirt1 (MUT), Choi and colleagues showed that overexpression of Sirt1 in astrocytes caused markedly increased food intake, body weight gain, and glucose intolerance, but expression of a deacetylase-deficient Sirt1 mutant decreased food intake and body weight and improved glucose tolerance, particularly in the females compared to the male animals. Interestingly, the effect of these Sirt1 mutants on insulin tolerance was reversed with overexpression showing greater insulin sensitivity. Mice overexpressing Sirt1 were more active, generated more heat, had elevated oxygen consumption, and the females were more sensitive to diet-induced obesity than males. Reproductively, the Sirt1 mutant mice had decreased ovulation. Findings from this research suggests Sirt1 signaling in astrocytes can contribute to metabolic and reproductive regulation.

SPOTLIGHT INVESTIGATOR: ELIZABETH RYAN

Elizabeth P. Ryan, Ph.D., is an associate professor in the College of Veterinary Medicine and Biomedical Sciences at Colorado State University and in the Department of Environmental Health in the Colorado School of Public Health. She is also a Member of the Cancer Control and Prevention division of the University of Colorado Cancer Center. She received her Ph.D. from the University of Rochester School of Medicine and Dentistry in Molecular Toxicology and Environmental Medicine. Her research demonstrates that rice bran and navy beans are functional foods for metabolism by the gut microbiome, which leads to production of bioactive metabolites for control and prevention of chronic disease. Ryan researches the application of dietary rice bran in developing and developed countries, and completed dose escalation, phase 0-1 feeding trials in infants, children, healthy adults and cancer survivors. She found that rice bran contains prebiotics and bioactive phytochemicals across diverse chemical classes while supplying essential amino acids and fatty acids to the host. She is investigating probiotic-fermented rice bran and developing functional fecal microbial transplants for prevention of colon cancer in high risk adults. Dr. Ryan and her colleagues received an R01, Rice Bran Microbial Metabolism for Colon Chemoprevention.

Read more about Dr. Ryan

Did you know?

Goji: A Vision of a Berry

The exotic oblong-shaped goji also known as wolfberry, is the fruit of the Lycium barbarum and Lycium chinense species, and traces back 2000 years to the Tang Dynasty. Traditional Chinese medicine uses it in soups, teas, wine, juices and tinctures for improved vision, infertility, inflammation and enhanced longevity. Goji is rich in phenolic acids, flavonoids, vitamin C, riboflavin and thiamine. Goji’s reputation for its vision-protective effects comes in part from its bioactive polysaccharides and unique carotenoid profile, including beta-carotene, lutein and dipalmitin zeaxanthin. This superfood is one of the most robust zeaxanthin food sources available!

Fresh bright red goji berries are harvested in late summer-early autumn, though goji powder or the sun-dried berries are more readily available. Raw goji berries are reminiscent of a raisin with a distinct cranberry-like tang that goes a long way in flavor. To savor chewier goji berries, soak them in water for 5-10 minutes and fold them into rice, quinoa, oatmeal or yogurt. This summer when you think of berries, consider adding this “vision of a berry” to your day for a boost of fiber and take your smoothie, breakfast bowl and other eclectic dishes to the next level in flavor and nutrients!