1) The document discusses nutrigenomics research on the effects of different types of dietary fats on human health. Certain long chain saturated fats are described as potentially pro-inflammatory, while unsaturated fats like omega-3 PUFAs are anti-inflammatory.
2) Studies in mice found that a high-fat diet led to heterogeneity in liver responses, with some mice developing non-alcoholic steatohepatitis (NASH) due to interactions between dysfunctional adipose tissue and the liver. Certain plasma proteins were identified as potential early biomarkers for NASH.
3) Human studies found that saturated fat-rich diets induced pro-inflammatory gene expression in adipose tissue and blood cells
Call Girls Service Jaipur {9521753030} ❤️VVIP RIDDHI Call Girl in Jaipur Raja...
Nutrigenomics of FAT
1. Nutrigenomics of FAT: What is “good” or “bad” for human health? Michael MüllerNetherlands Nutrigenomics Centre & Nutrition, Metabolism and Genomics GroupDivision of Human Nutrition, Wageningen University
2. 2 Meals a day, work as long as possible & embrace challenge Walter Breuning (1896 - 2011)
4. Our “paleolithic” genes + modern diets Paleolithic era Modern Times 1.200.000 Generations between feast en famine 2-3 Generations in energy abundance % Energy % Energy 100 100 Grain Milk/-products Isolated Carbohydrates Isolated Fat/OilAlcohol Low-fat meatChicken Eggs Fish 50 Meat Chicken Fish 50 Fruit Vegetables (carrots) Nuts Honey Fruit Vegetables Beans 0 0
27. Role of macrophages in lipid metabolism (JBC 2008; Cell Metabolism 2010)hepatic steatosis steatohepatitis (NASH) & fibrosis cirrhosis
28. Interaction between WAT and liver tissue essential for NASH/NAFLD in C57Bl/6 mice Objective: Nonalcoholic fatty liver disease (NAFLD) is strongly linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aimed to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that predict NASH.
40. Conclusions Our data support the existence of a tight relationship between adipose tissue dysfunction and NASH pathogenesis. It points to several novel potential predictive biomarkers for NASH. Diabetes. 2010;59:3181-91.
47. ‘Obese-linked’ pro-inflammatory gene expression profile by SFAs MUFA diet SFA diet The SFA-rich diet: Induces a pro-inflammatory obese-linked gene expression profile Decreases expression and plasma level of the anti-inflammatory cytokine adiponectin “Personal Transcriptomes” Van Dijk et al. AJCN 2009
48. Fish-oil supplementation induces anti-inflammatory gene expression profiles in human blood mononuclear cells Less inflammation & decreased pro-arteriosclerosis markers= Anti-immuno-senescence Bouwens et al. Am J ClinNutr. 2009
49. Summary Less healthy: Dietary fats rich in long chain saturated fatty acids that can be pro-inflammatory if chronically “overconsumed” More favourable: Unsaturated fatty acids (in particular PUFAs from fish oil) have anti-inflammatory properties A healthy adipose tissue is essential to efficiently store fat and prevent ectopic fat deposition Healthy : Subcutanous fat > visceral fat > ectopic fat : Unhealthy Future challenge: To prevent the unhealthy effects of a surplus of added sugars (sucrose, fructose) & high GI carbs Will be converted into saturated fat Linked to ectopic fat deposition e.g. NASH Linked to obesity, diabetes, CVD…. Childhood obesity
50. Thanks Lydia Afman Mark Bouwens Susan van Dijk DiederikEsser Sergio Lopez Lisette de Groot Marianne Geleijnse Ondine van de Rest MariekeBos Edith Feskens RikHeijligenberg Dianne Hoelen Jeanne de Vries Geert Heidema
Editor's Notes
Inflammation has been associated with many disease phenotypes including steatohepatitis or diabetes. This relationship is in particular when inflammation is chronic or non-resolving. There is an interaction between metabolism and inflammation with positive or negative consequences with respect to organ and systemic health.In my talk I will briefly discuss two unpublished studies, one investigating the important interaction of WAT and liver in particular under conditions of diet-induced obesity. Organ-specific macrophages in WAT and liver play an crucial role in progressing organ-specific inflammatory phenotypes. In the second study we found very interesting interaction between dietary fat and macrophages in mesenteric lymph nodes that are exposed postprandially to very high concentrations of chylomicrons. We used a k.o. mouse for ANGPTL4 and could show that chronic consumption of saturated fat can be deadly.
A) Bodyweight changes in the 4 subgroups during the 21 week dietary intervention. White squares: LFL, Light grey squares: LFH, dark grey squares: HFL, black squares: HFH. B) Mean daily energy intake. C) Positive correlation between final bodyweight and liver triglyceride concentration (P<0.05). D) Weight of epididymal fat depot. E) Adipose tissue leptin mRNA expression as determined by qPCR. Mean expression in LFL mice was set at 100%. F) Plasma free fatty acid levels. Error bars reflect standard deviation. * = significantly different from HFL mice according to Student’s t-test (P<0.05). Number of mice per group: n=4 (LFL, HFL, HFH), n=6 (LFH).
A subpopulation of mice fed HFD develops NASH. Haematoxylin and eosin staining (D) and oil red O staining (E) of representative liver sections of the 4 subgroups
(Immuno)histochemical staining confirms enhanced inflammation and early fibrosis in HFH miceImmunohistochemical staining of macrophage activation in representative liver section of HFL and HFH mice using antibody against the specific macrophagemarker Cd68Collagen staining using fast green FCF/sirius red F3B. Staining of stellate cell activation using antibody against GFAP.
- Number of genes up- or down-regulated in the various subgroups in comparison to the LFL mice, as determined by Affymetrix GeneChip analysis. Genes with a p-value below 0.05 were considered significantly regulated. - Heat map showing changes in expression of selected genes involved in lipid metabolism, inflammation and fibrosis in liver. Changes in gene expression of selected genes as determined by real-time quantitative PCR. Mean expression in LFL mice was set at 100%. Error bars reflect standard deviation. Bars with different letters are statistically different (P<0.05 according to Student’s t-test). Number of mice per group: n=4 (LFL, HFL, HFH), n=6 (LFH).
Haematoxylin and eosin staining of representative adipose tissue sections. Immunohistochemical staining of macrophages using antibody against Cd68. Collagen staining using fast green FCF/sirius red F3B.
Adipose tissue mRNA expression of a selected group of genes was determined by quantitative real-time PCR after 21 weeks of dietary intervention. Mean expression in LFL mice was set at 100%. Error bars reflect standard deviation. * = significantly different from HFL mice according to Student’s t-test (P<0.05). Number of mice per group: n=4 (LFL, HFL, HFH), n=6 (LFH).
. A) Plasma concentration of haptoglobin, TIMP-1, IL-1β, leptin and insulin were determined by multiplex assay at specific time points during the 21 weeks of dietary intervention after a 6h fast. White squares: LFL, Light grey squares: LFH, dark grey squares: HFL, black squares: HFH. Error bars reflect standard deviation. * = significantly different from HFL mice according to Student’s t-test (P<0.05). Number of mice per group: n=4 (LFL, HFL, HFH), n=6 (LFH).