Reduced intestinal FADS1 gene expression and plasma omega-3 fatty acids following Roux-en-Y gastric bypass

Abstract

Roux-en-Y gastric bypass (RYGB) limits food ingestion and may alter the intestinal expression of genes involved in the endogenous synthesis of polyunsaturated fatty acids (PUFAs). These changes may decrease the systemic availability of bioactive PUFAs after RYGB. AIM: To study the impact of RYGB on the dietary ingestion and plasma concentration of PUFAs and on the intestinal expression of genes involved in their endogenous biosynthesis in severely obese women with type 2 diabetes. METHODS: Before, and 3 and 12 months after RYGB, obese women (n=20) self-reported a seven-day dietary record, answered a food frequency query and provided plasma samples for alpha-linolenic (ALA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and arachidonic (ARA) acid assessment by gas chromatography. Intestinal biopsies (duodenum, jejunum and ileum) were collected through double-balloon endoscopy before and 3 months after RYGB for gene expression analysis by microarray (Human GeneChip 1.0 ST array) and RT-qPCR validation. RESULTS: Compared to the preoperative period, patients had decreased intakes of PUFAs, fish and soybean oil (p<0.05) and lower plasma concentrations of ALA and EPA (p<0.001) 3 and 12 months after RYGB. FADS1 gene expression was lower in duodenum (RT-qPCR fold change=-1.620, p<0.05) and jejunum (RT-qPCR fold change=-1.549, p<0.05) 3 months following RYGB, compared to before surgery. CONCLUSION: RYGB decreased PUFA ingestion, plasma ALA and EPA levels, and intestinal expression of FADS1 gene. The latter encodes a key enzyme involved in endogenous biosynthesis of PUFAs. These data suggest that supplementation of omega-3 PUFAs may be required for obese patients undergoing RYGB.

The effect of a duodenal-jejunal bypass liner on lipid profile and blood concentrations of long chain polyunsaturated fatty acids

“…These reports, however, do conflict with respect to the changes observed. Our findings match those studies that report an overall decrease in serum or plasma long chain PUFAs following weight-loss surgery [31,48,50]. This is possibly a consequence of reduced dietary intake coupled with increased liberation from adipose stores and increased fatty acid oxidation during significant weight loss [31,49].…”

“…Several studies have reported on proportional changes in PUFAs (as opposed to absolute concentrations as reported in the current study) and observed that, although absolute concentrations of these fatty acids decreased, relative proportions were actually increased following metabolic surgery, thus creating a more favourable lipid profile [29,48,51]. In the study by Walle et al, however, subjects were instructed to consume 3 teaspoons of rapeseed oil and 6 tea spoons of mainly rapeseed oil based spreads daily for at least 1e2 years after their weight loss operation and were instructed to consume fish 2e3 times a week.…”

“…This is supported by the observation that patients undergoing laparoscopic sleeve gastrectomy, in which there is no bypass of the small intestine, have less profound and sustained changes in fatty acid concentrations when compared to bypass procedures [31]. Garla et al [48] also propose that decreased intestinal expression of the fatty acid desaturase-1 (FADS1) gene, which encodes the delta-5 desaturates enzyme, may also be responsible, in part, for the observed reduction in EPA.…”

Western and heart healthy dietary patterns differentially affect the expression of genes associated with lipid metabolism, interferon signaling and inflammation in the jejunum of Ossabaw pigs

“…In our study, FADS1 gene expression was higher in pigs fed the HHD compared to the WD in the jejunal mucosa, and these data were consistent with the estimated D5D enzyme activity in serum. The FADS1 gene encodes for the delta-5 desaturase protein that converts dihomo-gamma-linoleic acid (20:3 n-6, DGLA) to arachidonic acid (20:4 n-6, ARA) and eicosatetraenoic acid (20:4 n-3, ETA) to eicosapentaenoic acid (20:5 n-3, EPA) [ 41 ]. Altered estimated enzyme activity or expression of FADS1 gene has been implied in several disease states, including CAD and insulin resistance [ 42 , 43 ].…”

Increased Cellular Uptake of Polyunsaturated Fatty Acids and Phytosterols from Natural Micellar Oil

“…Under pathophysiological conditions of fat malabsorption, however, micellization of lipophilic compounds might become especially important for supplementation with essential fatty acids. Fat malabsorption occurs due to gastrointestinal diseases, such as Crohn's disease [35], exocrine pancreatic insufficiency [36], cystic fibrosis [37], or after gastric bypass surgery [38]. Similarly, the use of Orlistat, an anti-obesity drug that limits fat absorption by inhibition of pancreatic lipase, leads to fat malabsorption [39].…”