Effect of an Asian-adapted Mediterranean diet and pentadecanoic acid on fatty liver disease: the TANGO randomized controlled trial.

BACKGROUND: Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD. OBJECTIVES: To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD. METHODS: In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed. RESULTS: In the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss. CONCLUSION: Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome. TRIAL REGISTRATION NUMBER: This trial was registered at the clinicaltrials.gov as NCT05259475.

Increased Consumption of Unsaturated Fatty Acids Improves Body Composition in a Hypercholesterolemic Chinese Population.

While an increase in fat intake and the resulting excess calorie intake are implicated in weight gain, different fat types exert variable effects on body composition, with unsaturated fats showing favorable effects on body composition in Western population. Whether and to what extent these associations apply to Asian population have not been established. We investigated the effects of two separate Asian-based oil blends, rich in unsaturated fats, made from refined rice bran, sesame, and flaxseed oils, in comparison with refined olive oil, on body composition using dual-energy X-ray absorptiometry (DXA), from an 8-week, parallel design, randomized trial in 66 men (58.7 ± 5.71 years old, 23.0 ± 2.38 kg/m2) and 69 postmenopausal women (59.1 ± 5.34 years old, 21.7 ± 2.52 kg/m2), with borderline hypercholesterolemia. Despite increases in mean daily intakes of total energy (approximately +400 kcal/day, female, and approximately +240 kcal/day, male), as well as increases in percentage of calories from fats and proteins and decreases in percentage of calories from carbohydrates during the dietary intervention period, there were no significant changes in total body fat mass in both genders and also in all treatment groups. While total body weight increased slightly (0.36 ± 0.12 kg, p = 0.005) in women during intervention, this was mainly due to gain in lean mass (0.38 ± 0.081 kg, p < 0.0001). Correspondingly, there were reductions in total body fat (%), android fat (%), and gynoid fat (%) in women. No significant differences between the 3 intervention oil types were found in any of the measured parameters in either gender. Increasing relative intakes of unsaturated fats may prevent fat mass gain and circumvent muscle mass loss associated with menopause in older Asian women. Long-term studies are needed to confirm findings. This study had been registered on clinicaltrials.gov (Identifier No.: NCT03964857, https://www.clinicaltrials.gov/ct2/show/NCT03964857).

Gut microbiome responses to dietary intervention with hypocholesterolemic vegetable oils.

Hypercholesterolemia is becoming a problem with increasing significance. Dietary vegetable oils may help to improve this condition due to presence of phytonutrients with potentially synergistic cholesterol-lowering effects. The objective of this 8-week double-blinded randomized clinical trial was to investigate the effects of consuming 30 g of two different blended cooking oils, rich in omega-3 alpha-linolenic acid and phytonutrients, or refined olive oil on the intestinal microbiota in 126 volunteers with borderline hypercholesterolemia. Multi-factor analysis of relationships between the gut microbiota composition at various taxonomic ranks and the clinical trial parameters revealed the association between beneficial effects of the dietary intervention on the blood lipid profile with abundance of Clostridia class of the gut microbiota. This microbiota feature was upregulated in the course of the dietary intervention and associated with various plasma markers of metabolic health status, such as Triglycerides, Apolipoprotein B and Total Cholesterol to HDL ratio in a beneficial way. The relative abundance of a single species-Clostridium leptum-highly increased during the dietary intervention in all the three study groups. The oil blend with the highest concentration of omega-3 PUFA is associated with faster and more robust responses of the intestinal microbiota, including elevation of alpha-diversity. Butyrate production is being discussed as a plausible process mediating the observed beneficial influence on the plasma lipid profile. Causal mediation analysis suggested that Clostridium genus rather than the higher rank of the phylogeny-Clostridia class-may be involved in the diet-induced improvements of the blood lipid profile.

Two Blends of Refined Rice Bran, Flaxseed, and Sesame Seed Oils Affect the Blood Lipid Profile of Chinese Adults with Borderline Hypercholesterolemia to a Similar Extent as Refined Olive Oil.

BACKGROUND: Individual vegetable oils have a characteristic fatty acids (FA) composition and unique phytonutrient profiles, enabling formulation of oil blends that may have health-promoting effects. OBJECTIVE: The primary objective of this study was to investigate effects of 2 oil blends made with refined rice bran, flaxseed, and sesame oils, with distinct monounsaturated to saturated FA, polyunsaturated to saturated FA, and omega-3 (n-3) to omega-6 FA ratios and different phytonutrient concentrations on blood lipid profile, compared with refined olive oil as a control. The secondary outcomes were other markers of cardiometabolic health. METHODS: A parallel-design, randomized controlled trial compared consumption of 30 g of allocated intervention oil per day for a period of 8 wk. The study recruited 143 borderline hypercholesterolemic (LDL cholesterol: 3.06-4.51 mmol/L) Chinese volunteers between 50 and 70 y old and with a BMI (kg/m2) ≤27.5. All outcomes were measured every 2 wk, and the time × treatment interactions and the main effects of treatment and time were analyzed using an intention-to-treat approach. RESULTS: Compared with baseline (week 0), there were significant reductions during the post-intervention time points in serum total cholesterol (-3.47%; P < 0.0001), LDL cholesterol (-4.16%; P < 0.0001), triglycerides (-10.3%; P < 0.0001), apoB (-3.93%; P < 0.0001), total to HDL-cholesterol (-3.44%; P < 0.0001) and apoB to apoA1 (-3.99%; P < 0.0001) ratios, systolic and diastolic blood pressures (-3.32% and -3.16%, respectively; both P < 0.0001), and serum glucose (-1.51%; P < 0.05) and a small but significant increase in body weight (+0.7%; P < 0.001) for all 3 intervention oils but no effects of intervention on HDL-cholesterol or apoA1 concentration. No significant effects of treatment or time × treatment interactions were found. CONCLUSIONS: Using blended vegetable oils that are extensively consumed in Asia, this study found that specific oil blends can improve blood lipid profile and other cardiometabolic parameters, to a similar extent as refined olive oil, in Chinese adults with borderline hypercholesterolemia. This trial is registered at www.clinicaltrials.gov as NCT03964857.

Spatially resolved microrheology of heterogeneous biopolymer hydrogels using covalently bound microspheres.

Characterization of the rheological properties of heterogeneous biopolymers is important not only to understand the effect of substrate elasticity on cell behaviors, but also to provide insights into mechanical changes during cellular remodeling of the environment. Conventional particle-tracking microrheology (PTM) techniques are compromised by probe-network slippage and cage-hopping problems, and require a priori knowledge of network mesh size in order to determine a suitable probe size. We demonstrated here the usefulness of covalently bound probes for PTM of biopolymers to overcome the above limitations. We showed that, in a well-defined system like polyacrylamide gels, surface-modified probe particles using a zero-length crosslinker provided more reliable measurements of network mechanics as compared to standard carboxylated probes. We further demonstrated that appropriate surface modification of microspheres for PTM circumvented the requirement of using microspheres larger than the network mesh, an approach typically considered to be ideal. Using the method presented in this study, we found the local network at the leading edge of a typical C6 glioma cell to be stiffer as compared to the side. Our findings established that permanent interaction between the probe and network is crucial to reliably measure the local network mechanics in reconstituted, heterogeneous networks using PTM.

Early stiffening and softening of collagen: interplay of deformation mechanisms in biopolymer networks.

Collagen networks, the main structural/mechanical elements in biological tissues, increasingly serve as biomimetic scaffolds for cell behavioral studies, assays, and tissue engineering, and yet their full spectrum of nonlinear behavior remains unclear. Here, with self-assembled type-I collagen as model, we use metrics beyond those in standard single-harmonic analysis of rheological measurements to reveal strain-softening and strain-stiffening of collagen networks both in instantaneous responses and at steady state. The results show how different deformation mechanisms, such as deformation-induced increase in the elastically active fibrils, nonlinear extension of individual fibrils, and slips in the physical cross-links in the network, can lead to the observed complex nonlinearity. We demonstrate how comprehensive rheological analyses can uncover the rich mechanical properties of biopolymer networks, including the above-mentioned softening as well as an early strain-stiffening, which are important for understanding physiological response of biological materials to mechanical loading.