Obesity and dyslipidemia are hallmarks of metabolic and cardiovascular diseases. Polydextrose (PDX), a soluble fiber has lipid lowering effects. We hypothesize that PDX reduces triglycerides and cholesterol by influencing gut microbiota, which in turn modulate intestinal gene expression. C57BL/6 male mice were fed a Western diet (WD) ±75 mg PDX twice daily by oral gavage for 14 days. Body weight and food intake were monitored daily. Fasting plasma lipids, caecal microbiota and gene expression in intestine and liver were measured after 14 days of feeding. PDX supplementation to WD significantly reduced food intake (p < 0.001), fasting plasma triglyceride (p < 0.001) and total cholesterol (p < 0.05). Microbiome analysis revealed that the relative abundance of Allobaculum, Bifidobacterium and Coriobacteriaceae taxa associated with lean phenotype, increased in WD + PDX mice. Gene expression analysis with linear mixed-effects model showed consistent downregulation of Dgat1, Cd36, Fiaf and upregulation of Fxr in duodenum, jejunum, ileum and colon in WD + PDX mice. Spearman correlations indicated that genera enriched in WD + PDX mice inversely correlated with fasting lipids and downregulated genes Dgat1, Cd36 and Fiaf while positively with upregulated gene Fxr. These results suggest that PDX in mice fed WD promoted systemic changes via regulation of the gut microbiota and gene expression in intestinal tract.

Background Postprandial lipemia is a risk factor for cardiovascular disease. Dairy products differ in nutrient content and food matrix, and little is known about how different dairy products affect postprandial triglyceride (TG) concentrations. Objective We investigated the effect of meals with similar amounts of fat from different dairy products on postprandial TG concentrations over 6 h in healthy adults. Methods A randomized controlled cross-over study was performed on 47 subjects (30% men), with median (25th–75th percentile) age of 32 (25–46) y and body mass index of 23.6 (21.0–25.8) kg/m2. Meals included 1 of butter, cheese, whipped cream, or sour cream, corresponding to 45 g of fat (approximately 60 energy%). Serum concentrations of TGs (primary outcome), and total cholesterol (TC), low density lipoprotein cholesterol (LDL cholesterol), high density lipoprotein cholesterol (HDL cholesterol), insulin, glucose, non-esterified fatty acids, and plasma glucose-dependent insulinotropic polypeptide (secondary outcomes) were measured before the meal and 2, 4, and 6 h postprandially. Incremental AUC (iAUC) was calculated for the responses, and data were analyzed using a linear mixed model. Results Sour cream induced a 61% larger TG-iAUC0–6 h compared to whipped cream (P < 0.001), a 53% larger TG-iAUC0–6 h compared to butter (P < 0.001), and a 23% larger TG-iAUC0–6 h compared to cheese (P = 0.05). No differences in TG-iAUC0–6 h between the other meals were observed. Intake of sour cream induced a larger HDL cholesterol-iAUC0–6 h compared to cheese (P = 0.01). Intake of cheese induced a 124% larger insulin iAUC0–6 h compared to butter (P = 0.006). No other meal effects were observed. Conclusions High-fat meals containing similar amount of fat from different dairy products induce different postprandial effects on serum TGs, HDL cholesterol, and insulin in healthy adults. The potential mechanisms and clinical impact of our findings remain to be further elucidated. The study was registered at www.clinicaltrials.gov as NCT02836106.

Insoluble residue (INS) is a lignin-rich fraction of brewer's spent grain (BSG) that also contains β-glucan and arabinoxylan, the major constituents of dietary fiber. We investigated the effects of INS in diet-induced obese mice in terms of lipid metabolism and metabolic diseases. Male mice (C57bl6) were fed a high-fat diet (HFD), a HFD + 20% INS, a HFD + 20% cellulose (CEL), a HFD with a combination of 20% INS−CEL (1:1), or a control diet for 14 weeks. Insulin and glucose tolerance tests were performed after 12 weeks. Fasting plasma lipids, bile acid, and fecal bile acid were measured after 14 weeks of feeding, and tissues were collected for gene expression analysis. Body weight gain was significantly reduced with all fibers, but only INS and INS−CEL decreased fasting plasma low-density lipoprotein cholesterol and total cholesterol compared to HFD. CEL and INS−CEL significantly improved insulin resistance. Fecal bile acids were significantly increased by all fibers, but there was no change in plasma bile acid. Clostridium leptum was increased with all fibers, but universal bacterial diversity was only with INS and INS−CEL. In addition, INS significantly increased the abundance of Bacteriodes, while CEL decreased Atopobium and Lactobacillus. INS feeding significantly upregulated various genes of cholesterol and bile acid metabolism, such as Srebp2, Hmgcr, Ldlr, Cyp7a1, Pparα, Fxr, and Pxr, in the liver. INS, INS−CEL, and CEL significantly attenuated liver steatosis. Our results suggest that INS from BSG induced beneficial systemic changes in mice via gut microbiota, bile acids, and gene expression in the liver.

Inflammation plays a significant role in pathogenesis of diabetes and atherosclerosis. Increased adiposity with an upregulation of cytokines in prediabetes has been associated with vascular inflammation and considered a leading causal factor for type 2 diabetes (T2D). Information on adipokines and inflammatory markers in prediabetes, defined by hemoglobin A1C (HbA1c) 5.7–6.4% in addition to impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), are sparse. We conducted a population–based cross-sectional study (part of a follow-up study) of inhabitants of Oulu, Finland, born in 1935. Inflammatory markers and traditional risk markers of 367 subjects were measured. The glucose status was determined by an oral glucose tolerance test (OGTT) and HbA1c. Inflammatory markers and glycemic levels were analysed using analysis of covariance (ANCOVA). Of the participants, 193 were normoglycemic, 82 had prediabetes and 40 T2D. Inflammatory cytokines were significantly higher in subjects with prediabetes as compared to normoglycemic subjects: IL-4 (14.9 vs 5.9 pg/ml, p = 0.041), IP-10 (251 vs 209 pg/ml, p = 0.05), TNF-α (10.4 vs 6.9 pg/ml, p = 0.027), RANTES (43.3 vs 33.1 pg/ml, p = 0.009), CD40L (3708 vs 1671 pg/ml, p = 0.010) and VEGF (269 vs 174 pg/ml, p = 0.013). These inflammatory cytokines remained significant even after adjustment for waist circumference. The differences in inflammatory markers in prediabetic and T2D subjects were not statistically significant. Prediabetes was associated with low-grade inflammation with increased inflammatory cytokine levels, while the levels in prediabetic subjects were comparable to those in T2D subjects. The associations were independent of visceral adiposity.