Background: Replacing SFAs with vegetable PUFAs has cardiometabolic benefits, but the effects on liver fat are unknown. Increased dietary n-6 PUFAs h

Excess ectopic fat storage is linked to type 2 diabetes. The importance of dietary fat composition for ectopic fat storage in humans is unknown. We investigated liver fat accumulation and body composition during overfeeding saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs). LIPOGAIN was a double-blind, parallel-group, randomized trial. Thirty-nine young and normal-weight individuals were overfed muffins high in SFAs (palm oil) or n-6 PUFAs (sunflower oil) for 7 weeks. Liver fat, visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT), total adipose tissue, pancreatic fat, and lean tissue were assessed by magnetic resonance imaging. Transcriptomics were performed in SAT. Both groups gained similar weight. SFAs, however, markedly increased liver fat compared with PUFAs and caused a twofold larger increase in VAT than PUFAs. Conversely, PUFAs caused a nearly threefold larger increase in lean tissue than SFAs. Increase in liver fat directly correlated with changes in plasma SFAs and inversely with PUFAs. Genes involved in regulating energy dissipation, insulin resistance, body composition, and fat-cell differentiation in SAT were differentially regulated between diets, and associated with increased PUFAs in SAT. In conclusion, overeating SFAs promotes hepatic and visceral fat storage, whereas excess energy from PUFAs may instead promote lean tissue in healthy humans.

OBJECTIVE—Conjugated linoleic acid (CLA) is a group of dietary fatty acids with antiobesity and antidiabetic effects in some animals. The trans10cis12 (t10c12) CLA isomer seems to cause these effects, including improved insulin sensitivity. Whether such isomer-specific effects occur in humans is unknown. The aim of this study was to investigate whether t10c12 CLA or a commercial CLA mixture could improve insulin sensitivity, lipid metabolism, or body composition in obese men with signs of the metabolic syndrome. RESEARCH DESIGN AND METHODS—In a randomized, double-blind controlled trial, abdominally obese men (n = 60) were treated with 3.4 g/day CLA (isomer mixture), purified t10c12 CLA, or placebo. Euglycemic-hyperinsulinemic clamp, serum hormones, lipids, and anthropometry were assessed before and after 12 weeks of treatment. RESULTS—Baseline metabolic status was similar between groups. Unexpectedly, t10c12 CLA increased insulin resistance (19%; P < 0.01) and glycemia (4%; P < 0.001) and reduced HDL cholesterol (−4%; P < 0.01) compared with placebo, whereas body fat, sagittal abdominal diameter, and weight decreased versus baseline, but the difference was not significantly different from placebo. The CLA mixture did not change glucose metabolism, body composition, or weight compared with placebo but lowered HDL cholesterol (−2%; P < 0.05). CONCLUSIONS—These results reveal important isomer-specific metabolic actions of CLA in abdominally obese humans. A CLA-induced insulin resistance has previously been described only in lipodystrophic mice. Considering the use of CLA-supplements among obese individuals, it is important to clarify the clinical consequences of these results, but they also provide physiological insights into the role of specific dietary fatty acids as modulators of insulin resistance in humans.

Background: Desaturase indexes, as markers of endogenous fatty acid desaturation, and a characteristic serum fatty acid (FA) composition are related to cardiovascular and metabolic diseases, but the relation to mortality is poorly investigated. Objective: The objective was to evaluate the relation between dietary fat biomarkers, desaturase indexes, and mortality. Design: In this community-based prospective sample, 50-y-old men were followed for a maximum of 33.7 y. Cox proportional hazard analysis was conducted to investigate desaturase indexes (stearoyl-CoA-desaturase and Δ⁶- and Δ⁵-desaturase) and the relation of individual serum esterified fatty acids (FAs) in relation to total and cardiovascular mortality in the total study sample (n = 2009) and in a healthy subsample (n = 1885). Desaturase indexes were estimated as product-to-precursor FA ratios. Results: During follow-up, 1012 men in the total sample died and 931 men in the healthy subsample died. Desaturase indexes predicted both total and cardiovascular mortality. The relations were independent of smoking status, physical activity, BMI, total cholesterol, and hypertension. The adjusted and standardized (per SD) hazard ratios (HRs) and 95% CIs for cardiovascular mortality were 1.15 (1.04, 1.27) for stearoyl-CoA-desaturase, 1.12 (1.0, 1.24) for Δ⁶-desaturase, and 0.88 (0.80, 0.98) for Δ⁵-desaturase, respectively. The proportion of serum linoleic acid was inversely related, whereas serum FAs associated with saturated fat intake (palmitic, palmitoleic, and dihomo-γ-linolenic acids) were directly related to total and cardiovascular mortality. Conclusions: Altered endogenous FA desaturation might contribute to mortality risk because we observed independent associations between desaturase activity indexes and mortality. The proportion of linoleic acid was inversely related, and FAs reflecting saturated fat intake were directly related to mortality.

Background— Conjugated linoleic acids (CLAs), a group of fatty acids shown to have beneficial effects in animals, are also used as weight loss supplements. Recently, we reported that the t 10 c 12 CLA-isomer caused insulin resistance in abdominally obese men via unknown mechanisms. The aim of the present study was to examine whether CLA has isomer-specific effects on oxidative stress or inflammatory biomarkers and to investigate the relationship between these factors and induced insulin resistance. Methods and Results— In a double-blind placebo-controlled trial, 60 men with metabolic syndrome were randomized to one of 3 groups receiving t 10 c 12 CLA, a CLA mixture, or placebo for 12 weeks. Insulin sensitivity (euglycemic clamp), serum lipids, in vivo lipid peroxidation (determined as urinary 8-iso-PGF _2α [F2-isoprostanes]), 15-ketodihydro PGF _2α , plasma vitamin E, plasma C-reactive protein, tumor necrosis factor-α, and interleukin-6 were assessed before and after treatment. Supplementation with t 10 c 12 CLA markedly increased 8-iso-PGF _2α (578%) and C-reactive protein (110%) compared with placebo ( P <0.0001 and P <0.01, respectively) and independent of changes in hyperglycemia or dyslipidemia. The increases in 8-iso-PGF _2α , but not in C-reactive protein, were significantly and independently related to aggravated insulin resistance. Oxidative stress was related to increased vitamin E levels, suggesting a compensatory mechanism. Conclusions— t 10 c 12 CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men. The oxidative stress seems closely related to induced insulin resistance, suggesting a link between the fatty acid-induced lipid peroxidation seen in the present study and insulin resistance. These unfavorable effects of t 10 c 12 CLA might be of clinical importance with regard to cardiovascular disease, in consideration of the widespread use of dietary supplements containing this fatty acid.