CPT1A Missense Mutation Associated With Fatty Acid Metabolism and Reduced Height in Greenlanders.

BACKGROUND: Inuit have lived for thousands of years in an extremely cold environment on a diet dominated by marine-derived fat. To investigate how this selective pressure has affected the genetic regulation of fatty acid metabolism, we assessed 233 serum metabolic phenotypes in a population-based sample of 1570 Greenlanders. METHODS AND RESULTS: Using array-based and targeted genotyping, we found that rs80356779, a p.Pro479Leu variant in CPT1A, was strongly associated with markers of n-3 fatty acid metabolism, including degree of unsaturation (P=1.16×10-34), levels of polyunsaturated fatty acids, n-3 fatty acids, and docosahexaoenic acid relative to total fatty acid levels (P=2.35×10-15, P=4.02×10-19, and P=7.92×10-27). The derived allele (L479) occurred at a frequency of 76.2% in our sample while being absent in most other populations, and we found strong signatures of positive selection at the locus. Furthermore, we found that each copy of L479 reduced height by an average of 2.1 cm (P=1.04×10-9). In exome sequencing data from a sister population, the Nunavik Inuit, we found no other likely causal candidate variant than rs80356779. CONCLUSION: Our study shows that a common CPT1A missense mutation is strongly associated with a range of metabolic phenotypes and reduced height in Greenlanders. These findings are important from a public health perspective and highlight the usefulness of complex trait genetic studies in isolated populations.

Smoking and red blood cell phospholipid membrane fatty acids.

Smoking is associated with lower n-3 long chain polyunsaturated fatty acids (LCPUFA) concentrations; however, limited studies have accounted for dietary PUFA intake or whether tobacco dose or smoking duration influences this association. We measured red blood cell phospholipid (RBC) membrane concentrations of fatty acids in 126 current smokers, 311 former smokers, and 461 never smokers using gas liquid chromatography and tandem mass spectrometry. Smokers had lower RBC membrane percentages of total n-3 LCPUFAs compared to former smokers or never smokers (median percent: 5.46, [interquartile range (IQR) 4.52, 6.28] versus 6.39; [IQR: 5.18, 7.85] versus 6.59; [IQR 5.34, 8.01]) (p<0.001) and this association remained after adjusting for dietary PUFA intake. Duration of smoking and cigarettes per day were not associated with RBC membrane n-3 LCPUFA differences. Smoking is associated with lower n-3 LCPUFA RBC membrane percentages and this association was not influenced by diet or smoking dose or duration.

Effect of early enteral nutrition with ω-3 polyunsaturated fatty acid on nutritional status and body immunity of postoperative patients with colorectal cancer / 中国医师进修杂志

Objective To study the effect of early enteral nutrition (EEN) with ω-3 polyunsaturated fatty acid on nutritional status and body immunity of postoperative patients with colorectal cancer.Methods Forty patients with colorectal cancer were randomly divided into EEN group and parenteral nutrition (PN) group by systematic sampling method with 20 cases of each.The patients in EEN group were given complete enteral nutrition with ω-3 polyunsaturated fatty acid 1-7 d after operation,while the patients in PN group only were given nutrient by regular PN.Nutritional status,body immunity before operation and 1-7 d after operation,and intestinal function recovery time,untoward reaction were determined.Results The postoperative anus first exhaust time and defecate time of patients in EEN group were significantly shorter than those in PN group [(48.0±5.6) hvs.(51.0±6.7) h,(53.0±4.8) h vs.(72.0±3.6) h,P＜0.05].Serum albumin and prealbumin 1 d after operation in 2 groups were significantly lower than before operation (P ＜0.05),but 7 d after operation were significantly higher than 1 d after operation (P ＜0.05).Serum albumin and prealbumin 7 d after operation in EEN group were significantly higher than PN group(P ＜ 0.05).IgG,IgA,IgM,CD3,CD4,CD8,CD4/CD8 1 d after operation in 2 groups were significantly lower than before operation (P ＜ 0.05).IgG,IgA,CD4,CD4/CD8 7 d after operation in EEN group were significantly higher than PN group (P＜ 0.05).Conclusions Compared with the PN,EEN with ω-3 polyunsaturated fatty acid can remarkably improve nutritional status and body immunity in postoperative patients with colorectal cancer.It can accelerate the recovery of intestine function and worthy of recommending.

Serum omega-3 polyunsaturated fatty acid and insulin resistance in type 2 diabetes mellitus and non-alcoholic fatty liver disease / 中华内科杂志

Objective To investigate the relationship between serum omega-3 polyunsaturated fatty acid (ω-3PUFA) and insulin resistance(IR) in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease (NAFLD). Methods This trial involved 51 patients of type 2 diabetes mellitus with NAFLD (G4 group), 50 patients of type 2 diabetes alone(G3 group), 45 patients of NAFLD alone (G2 group) and 42 healthy control subjects (G1 group). Serum ω-3PUFA profile was analyzed with capillary gas chromatography. Insulin resistance was assessed by homeostasis model assessment (HOMA-IR). ALT, AST, γ-glutamyltransferase(GGT) and serum lipids were measured. Results The levels of HOMA-IR were higher in G4 group than those in G3, G2 and G1 group(4. 90 ± 2. 54 vs 2. 38 ± 1.23, 2. 20 ± 1.15, 1.13± 0.42;P<0.05). The level of ALT, AST, GGT, TC, TG, LDL-C were higher in G4 group than those in G3, G2 and G1 group(P < 0. 05). The level of ω-3PUFA was signifieantly lower in G4 group than those in G3, G2 and G1 group(5.68 ±2.02 vs 7. 17 ±2. 38, 6.97±2.32, 10.08±2.76;P <0.05). ω-3PUFA cocentration was negatively correlated with HOMA-IR, TC, TG and LDL-C (r = -0.491, -0. 376, - 0. 462, - 0. 408, P < 0. 05). Conclusions Serum ω-3 PUFA is significantly decreased in patients with type 2 diabetes mellitus and NAFLD. Serum ω-3PUFA is negatively correlated with insulin resistance. ω-3PUEA plays a very important role in the development of diabetes mellitus and NAFLD.