Recipient Organization
UNIV OF CONNECTICUT
438 WHITNEY RD EXTENSION UNIT 1133
STORRS,CT 06269
Performing Department
Nutritional Sciences
Non Technical Summary
Obesity is a state of metabolic dysfunctions and chronic low-grade inflammation, which are causally linked to obesity co-morbidities, such as nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. We have sought the identification of new agricultural crops that may be consumed to combat obesity and its associated diseases. Edible brown seaweeds exert anti-obesity, anti-hyperlipidemic, and anti-diabetic activities. Therefore, there has been a growing interest in the health benefits of seaweed products in the U.S., consequently expanding seaweed farming in the eastern coastal states. However, studies on the health benefits of U.S.-grown seaweed are very limited. Our recent study provides evidence that consumption of sugar kelp (Saccharina latissima), a major edible brown alga grown in the U.S., prevents the development of obesity and its associated metabolic disturbances, inflammation, and fibrosis in the liver and white adipose tissue of diet-induced obesitymice. Interestingly, mice fed sugar kelp exhibited drastic alterations in the gut microbiome, which has an enormous impact on the host's energy metabolism. Also, polysaccharides in brown seaweeds act as prebiotics. Therefore, our preliminary findings indicate a potential contribution of the gut microbiota to the health benefits of sugar kelp. We will study in the project whether sugar kelp consumption prevents obesity and its associated abnormalities by altering the gut microbiota whose metabolites enhance energy expenditure by facilitating browning of white adipose tissue and increasingfecal energy excretion due to its high fiber content. Also, as concerns on potential adverse effects of iodine and heavy metals exist with sugar kelp consumption, we will evaluate their toxicity in vivo.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
With the increasing obesity epidemic, obesity co-morbidities are major health problems worldwide. It is crucial to identify U.S.-grown crops that can combat obesity-associated disorders. As edible brown seaweeds exert various health-promoting effects, seaweed farming for human consumption has been expanding in the U.S. However, studies on health benefits and safety of U.S.-grown seaweed is limited. The primary goal of this proposal is to evaluate whether consumption of U.S.-grown sugar kelp can counteract high fat-induced metabolic and inflammatory stresses with elucidating mechanisms, focusing on the contribution of the gut microbiota to the health benefits of sugar kelp. To achieve the goal, we will determine the role of the gut microbiota in the antagonistic effect of sugar kelp on obesity and its associated metabolic dysfunctions and inflammation in the liver and white adipose tissue (WAT) of diet-induced obesity mice. Particularly, we will assess the roles of sugar kelp in modulating energy expenditure via WAT browning and changing fecal energy excretion. Furthermore, we will evaluate iodine and heavy metal toxicity in vivo. Therefore, results from this study will be directly applicable to U.S. agriculture and will provide scientific evidence on the health benefits and safety of U.S.-grown sugar kelp to establish dietary recommendation of sugar kelp for the prevention of obesity-associated metabolic and inflammatory diseases. This study reflects the priority of the Food and Human Health Program priority, "Investigate the role of the food components or contaminants on the human gut microbiome and its metabolites, and the subsequent impact on human health."
Project Methods
Male and female C57BL/6J mice at the age of 8 wk will be fed AIN-96M low-fat (LF; 6% fat by wt), high-fat/high-sucrose/high-cholesterol (HF; modified from Bio-Serve F1850; 34% fat, 34% sucrose, 2.0% cholesterol, w/w), HF-I (HF diet containing the same amount of iodine in 6% sugar kelp powder), or HF-Kelp (6.0% dried sugar kelp powder, w/w) for 14 weeks. Another set of mouse groups will be given antibiotic cocktails in drinking water to deplete commensal bacteria, as described (37,48,49). Body weight and food consumption will be recorded weekly. To evaluate whether the change in physical activity by sugar kelp are independent of body weight, Comprehensive Lab Animal Monitoring System (CLAMS) will be conducted before (week 3) and after (week 13) mouse body weights are significantly altered by sugar kelp. Mice will also be subjected to an EchoMRI to determine body composition at wk 3 and 13. After 14 wk on the experimental diets, blood, liver, thyroid gland, soleus muscle, gonadal vWAT, inguinal sWAT, BAT, feces, and cecal contents will be collected for the analyses proposed in Objective 1 and 2.Phenotypes: body, liver, and WAT weights; food consumption; serum and tissue lipidsNASH and adipose inflammation: expression of lipogenic, inflammatory genes (e.g., F4/80, CD68, TNFa, CCL2) and browning genes (e.g., UCP1); H&E staining; serum ALT; serum free fatty acids (FFA); serum TNFaGut metabolites: serum concentrations of SCFAs and BAsFecal energy excretion: Bomb calorimetry for fecal calories; fecal fat contentsCecal microbiome composition analysisIodine toxicity: Serum triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH); weight and H&E staining of the thyroid gland for goiter Heavy metal toxicity: mercury, arsenic, cadmium and lead accumulation in the liver, kidney, brain; organ weights (liver, spleen, heart, kidney, brain); serum ALT, AST and liver histology for hepatic injury; complete blood count (including RBC & WBC count, hemoglobin, hematocrit, etc.) for abnormalities in the hematological system; and serum BUN and creatine for renal injury. Adipocytes will be isolated from sWAT (inguinal) and vWAT (gonadal: epididymal for male and perigonadal for female) of mice fed an experimental diet. Immediately, they will be subjected to MitoStress tests using a Seahorse XF analyzer to determine their basal respiration, basal glycolysis, oxygen consumption rate/extracellular acidification rate ratios, ATP production, proton leak, and non-mitochondrial respiration. Mitochondrial DNA copy number will be measured by determining the mitochondrial gene/nuclear gene ratios. The cells will also be analyzed by quantitative realtime PCR for the genes involved in browning and mitochondrial biogenesis/functions such as UCP1 and PGC-1a. UCP-1 protein and citrate synthase activity will be measured as a proxy of browning and mitochondrial density, respectively.