The Soluble Fiber α-Cyclodextrin Does Not Increase the Fecal Losses of Dietary Fat in Adults-A Double-Blind, Randomized, Placebo-Controlled, Crossover Trial.

Background: α-Cyclodextrin (α-CD), a soluble dietary fiber, may improve abnormal plasma lipids and promote weight loss. Preliminary evidence suggests that it may exert these effects by binding dietary fat and reducing absorption; this has not been tested in humans. Objective: The primary objective was to test whether supplemental α-CD increases fecal content of dietary lipid in humans. Methods: This was a randomized, double-blind, placebo-controlled, crossover study completed at the Mayo Clinic. Eight healthy volunteers, 5 premenopausal women and 3 men ages 23-54 y with body mass index (BMI; kg/m2) 18-27, underwent 2 separate study visits with a ≥2-wk washout period. The first morning of each visit volunteers consumed a standardized breakfast (14.5% protein, 27.5% fat, 60% carbohydrate, and 1.5 kcal/mL) containing [14C]tripalmitin and [3H]triolein with 2 g of α-CD or placebo, followed by 2 g of α-CD or placebo per meal for 2 more days. Volunteers consumed 100 g/d of dietary fat. Feces were collected for 72 h after the labeled breakfast to measure radiotracer content and total fecal fat. Radiotracer appearance in plasma TGs was measured at intervals after the labeled meal as a secondary outcome. Results: Virtually no 3H radiotracer, but an average of ∼20% of the 14C radiotracer was recovered in fecal lipids, with no difference between α-CD and placebo. Total fecal fat content and radiotracer appearance in postprandial plasma TGs did not differ between the α-CD and placebo treatments. Plasma appearance of 14C-TG was 37% ± 14% less (P < 0.0001) than 3H-TG. Conclusions: α-CD supplementation did not increase loss of dietary lipid in stool or total fecal fat compared with placebo in healthy adults. Greater stool loss and lesser appearance in plasma TGs of tripalmitin-derived [14C] compared with triolein-derived [3H] TGs imply different metabolic handling of these 2 dietary fat tracers. This trial was registered at www.clinicaltrials.gov as NCT03002168.

Very-long-chain ω-3 fatty acid supplements and adipose tissue functions: a randomized controlled trial.

Background: Increased omega-3 (n-3) fatty acid consumption is reported to benefit patients with metabolic syndrome, possibly due to improved adipose tissue function.Objective: We tested the effects of high-dose, very-long-chain ω-3 fatty acids on adipose tissue inflammation and insulin regulation of lipolysis.Design: A double-blind, placebo-controlled study compared 6 mo of 3.9 g eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)/d (4.2 g total ω-3/d; n = 12) with a placebo (4.2 g oleate/d; n = 9) in insulin-resistant adults. Before and after treatment, the volunteers underwent adipose tissue biopsies to measure the total (CD68+), pro- (CD14+ = M1), and anti- (CD206+ = M2) inflammatory macrophages, crown-like structures, and senescent cells, as well as a 2-step pancreatic clamping with a [U-13C]palmitate infusion to determine the insulin concentration needed to suppress palmitate flux by 50% (IC50(palmitate)f).Results: In the ω-3 group, the EPA and DHA contributions to plasma free fatty acids increased (P = 0.0003 and P = 0.003, respectively), as did the EPA and DHA content in adipose tissue (P < 0.0001 and P < 0.0001, respectively). Despite increases in adipose and plasma EPA and DHA in the ω-3 group, there were no significant changes in the IC50(palmitate)f (19 ± 2 compared with 24 ± 3 µIU/mL), adipose macrophages (total: 31 ± 2/100 adipocytes compared with 33 ± 2/100 adipocytes; CD14+: 13 ± 2/100 adipocytes compared with 14 ± 2/100 adipocytes; CD206+: 28 ± 2/100 adipocytes compared with 29 ± 3/100 adipocytes), crown-like structures (1 ± 0/10 images compared with 1 ± 0/10 images), or senescent cells (4% ± 1% compared with 4% ± 1%). There were no changes in these outcomes in the placebo group.Conclusions: Six months of high-dose ω-3 supplementation raised plasma and adipose ω-3 fatty acid concentrations but had no beneficial effects on adipose tissue lipolysis or inflammation in insulin-resistant adults. This trial was registered at clinicaltrials.gov as NCT01686568.

Direct free fatty acid storage in different sized adipocytes from the same depot.

OBJECTIVE: Human adipocytes take up free fatty acids (FFA) directly from the circulation, even at times of high lipolytic activity. Whether these processes occurs simultaneously within the same cells or are partitioned between different cells, for example large and small cells, is unknown. METHODS: The direct FFA storage in subcutaneous fat in 13 adults were measured using a continuous infusion of [U-(13)C]palmitate and a bolus of [1-(14)C]palmitate followed 30 min later by abdominal and femoral adipose biopsies. The adipocytes were isolated by digestion procedures and separated into small, medium and large populations by differential floatation. RESULTS: Populations of adipocytes were isolated that were statistically and clinically (∼3 fold different) in size. Adipocyte lipid SA was not different between small, medium and large cells, therefore, FFA storage per unit lipid was not different. However, FFA storage rates were significantly (two to four times) greater per cell in large than small cells (P < 0.005). In summary, relative to lipid content, FFA storage rates are not different in large and small adipocytes, however, large cells have greater storage rates per cell. CONCLUSIONS: This suggests that the processes of FFA release and storage are taking place simultaneously in adipocytes.

Stimulation of adipogenesis, peroxisome proliferator-activated receptor-gamma (PPARgamma), and thyrotropin receptor by PPARgamma agonist in human orbital preadipocyte fibroblasts.

The symptoms and signs of Graves' ophthalmopathy (GO) result from both an accumulation of hydrated hyaluronan in the orbital muscles and connective tissues and an expansion of the orbital adipose tissues. Recent studies have suggested a link between the stimulation of adipogenesis within the orbit in GO and the expression in these tissues of TSH receptor (TSHR), the putative orbital autoantigen. To further investigate this association, we treated orbital fibroblasts from patients with GO with rosiglitazone, a thiazolidinedione agonist of the PPARgamma receptor that stimulates adipocyte differentiation. We found this compound to be a potent stimulator of functional TSHR expression as well as TSHR and PPARgamma mRNA levels in differentiated cultures. In addition, rosiglitazone treatment stimulated recruitment and differentiation of a subset of cells within these cultures into mature lipid-laden adipocytes. These results suggest that TSHR expression in GO orbital preadipocyte fibroblasts is linked to adipogenesis, and that ligation of the PPARgamma receptor results in differentiation of these cells. It is possible that endogenous PPARgamma ligands play a role in stimulating orbital adipogenesis in GO, and that future treatments may be aimed at antagonism of various components of the PPARgamma signaling system.