Nutrition Frontiers - Summer 2017

Date Posted: 

Wednesday, August 9, 2017

Volume 8, Issue 3

Dear Colleague,

The summer issue of Nutrition Frontiers showcases insulin-like growth factor and vitamin D in prostate cancer risk, bile acid and FXR inactivation and gender dissimilarity, and CerS6, a novel transcriptional target of p53 protein. Meet our spotlight investigator, Dr. Wendy Russell, and her research on the functional role of the gut microbiota. Learn about celery, the leafy stalk, upcoming announcements and more.


Insulin-Like Growth Factor Axis and Vitamin D in Prostate Cancer Risk

An image with olive oil, fish, eggs, and dairy products on a table.The insulin-like growth factor (IGF) axis may play a role in prostate cancer. Circulating IGF-1 has been associated with increased risk of advanced prostate cancer, and IGF binding proteins (IGFBP) may be associated with prostate cancer development or progression. Using a nested case-control design in a sub-study of the Prostate Cancer Prevention Trial, which examined the ability of finasteride to prevent prostate cancer, Miles and colleagues investigated whether IGF axis analytes modified the association of serum hydroxyvitamin D 25(OH)D with prostate cancer risk. Although there were no interactions between serum 25(OH)D and IGF analytes when treatment arms (finasteride and placebo) were combined, higher 25(OH)D was associated with an increased risk of prostate cancer in the presence of higher serum IGF-2 in the placebo arm, with a significant interaction between 25(OH)D and the treatment arm. Further, there was an interaction between the treatment arm and serum IGFBP-3. In the absence of finasteride treatment and under conditions of higher IGF-axis analytes, higher levels of serum 25(OH)D may increase prostate cancer risk. Thus, consideration of serum concentration of IGF analytes might be helpful for determining vitamin D intake levels, particularly for men at higher risk for prostate cancer.


The National Academies convened an ad hoc committee to determine guiding principles to support future DRI committees as they make decisions about recommending DRIs for specific or other food substances that could ameliorate the risk of chronic disease. The resulting report, Guiding Principles for Developing Dietary Reference Intakes Based on Chronic Disease, addresses conceptual and methodological challenges and offers recommendations and guiding principles to develop DRIs based on chronic disease endpoints.

Upcoming Events

August 28-31, 2017
NuGoweek 2017: Molecular Nutrition – Understanding How Food Influences Health
Varna, Bulgaria

October 21-24, 2017
Food and Nutrition Conference
and Expo

Chicago, IL

October 29-November 2, 2017
Obesity Week 2017
Washington, DC

November 8-10, 2017
Disrupting Cancer: The Role of Personalized Nutrition, American College of Nutrition’s 58th Annual Conference
Alexandria, Virginia

December 5-6, 2017
NIH Pathways to Prevention Workshop: Methods for Evaluating Natural Experiments in Obesity
Bethesda, MD


Bile Acid and FXR Inactivation May Account for Gender Dissimilarity in Metabolism

Image of a liver.Farnesoid X receptor (FXR) inactivation is associated with steatosis leading to cancer progression. Sheng, Jena and colleagues evaluated the dietary impact and FXR status in wild type and FXR knockout (KO) mice when fed either a control diet with 5% fat and 12% sucrose or a Western diet (WD) high in fat (21%) and carbohydrate (34%). They found male WD-fed FXR KO mice had the highest hepatic and lipid serum levels, and the most severe steatosis along with insulin-resistance compared to female mice. FXR inactivation resulted in increases in the gut bacteria, Desulfovibrionaceae, Deferribacteraceae, and Helicobacteraceae, and was positively correlated with increased hepatic taurine-conjugated cholic acid, β-muricholic acid and pro-inflammatory and tumor-promoting hepatic and serum lipids. This study suggests possible gender dissimilarity in metabolic diseases and a FXR-dependent relationship between gut microbiota, dysregulated bile acids, and metabolic diseases. Further studies are warranted to evaluate gender variations and possibly inform investigational strategy using probiotics for metabolic disease.

CerS6: A Novel Transcriptional Target of p53 Protein

Image of fat cells.Tumor suppressor p53 is commonly activated upon certain types of cellular stress. In lipid metabolism, p53 activates fatty acid oxidation and inhibits fatty acid synthesis, and it has been implicated in the regulation of sphingolipid metabolism, which is important for the structural integrity of cellular membranes and as signaling molecules involved in the regulation of major cellular processes. Ceramides are a group of sphingolipids and their biosynthesis in humans is accomplished by six ceramide synthases, CerS1-6, using acyl groups with different chain lengths. In a study by Fekry and colleagues CerS6 promoter is found to be regulated by p53. The Promo 3.0.2 online tool for the prediction of transcription factor binding sites indicated multiple putative p53 binding sites in the CerS6 promoter of a human lung carcinoma cell line. Treatment of cells with Nutlin-3 or low concentrations of actinomycin D resulted in strong elevation of CerS6 mRNA and protein and demonstrated that CerS6 transcription is induced upon p53 activation. By transcriptional activation of CerS6, p53 can activate ceramide biosynthesis which contributes to the pro-apoptotic cellular response.


Portrait of Wendy Russell, PhDWendy Russell, PhD heads the Gut Health theme at the University of Aberdeen Rowett Institute in Scotland. Having graduated in chemistry from the University of Bristol and specialized in molecular nutrition, she investigates the complex relationship between diet and human health. She studies the diet-derived metabolic phenotypes defining population groups and the impact of dietary modulation on non-communicable diseases. With a strong focus on the functional role of the gut microbiota, she is identifying metabolites that are likely to play a major part in modulating inflammation. For this work, Wendy was awarded a U01 for Identifying Microbial Metabolites and the Bacteria Responsible for their Formation to facilitate an understanding of the interplay between diet, the gut microbiome and human health. Wendy also has active research addressing local and global food security, particularly in terms of ensuring the supply chain is nutritionally resilient. She works across a wide range of stakeholders through leadership of food groups and with industry by chairing the International Life Science Institute expert groups.

Read more about Wendy Russell

Did You Know?

Celery:  The Leafy Stalk

An image of a celery stalk.A popular member of the Apiaceae family, celery (Apium graveolens L.) is native to the Mediterranean and Middle East region. In fact, the Romans used it medicinally as an aphrodisiac. Celery is a staple in the French mirepoix and a mainstay in hearty Louisiana Creole and Cajun cuisine. Celery's unique essential oils are found in its leaves (fronds), stalk (petiole), roots and in particular, its' seeds. The often overlooked fronds have a high portion of essential oils and aroma extracts that can add a bang to any dish and make a great addition to salads, smoothies and sandwiches.

Celery's many global varieties have slightly differing tastes and appearances, from the Celeriac variety in Europe to pliable leafy Chinese celery to the light green crisp petiole Pascal variety, found mainly in the U.S.  All varieties are teeming with vitamin C, carotene, amino acids, cellulose, and flavonoids, making celery a great culinary and health option.  Try these delicious celery recipes.

Culinary Tips:

  • Look for perky fronds (leaves) and light green unbruised stalks.
  • Renew "wilty" fronds by immersing in a glass of ice water for 30 minutes.
  • Keep your celery in plastic bag in the crisper drawer section of your refrigerator.