Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice.

Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota.

Yoghurt consumption is associated with changes in the composition of the human gut microbiome and metabolome.

Background: Yoghurt contains live bacteria that could contribute via modulation of the gut microbiota to its reported beneficial effects such as reduced body weight gain and lower incidence of type 2 diabetes. To date, the association between yoghurt consumption and the composition of the gut microbiota is underexplored. Here we used clinical variables, metabolomics, 16S rRNA and shotgun metagenomic sequencing data collected on over 1000 predominantly female UK twins to define the link between the gut microbiota and yoghurt-associated health benefits.

A posteriori dietary patterns better explain variations of the gut microbiome than individual markers in the American Gut Project.

Background: Individual diet components and specific dietary regimens have been shown to impact the gut microbiome.

Objectives: Here, we explored the contribution of long-term diet by searching for dietary patterns that would best associate with the gut microbiome in a population-based cohort.

Methods: Using a priori and a posteriori approaches, we constructed dietary patterns from an FFQ completed by 1800 adults in the American Gut Project.

Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials.

Objective: To systematically review the effect of oral intake of bacterial probiotics on 15 variables related to obesity, diabetes and non-alcoholic fatty liver disease.

Design: Systematic review and meta-analysis.

Data Sources: Medline, EMBASE and COCHRANE from 1990 to June 2018.

Opportunistic Infections in HIV-Infected Patients Differ Strongly in Frequencies and Spectra between Patients with Low CD4+ Cell Counts Examined Postmortem and Compensated Patients Examined Antemortem Irrespective of the HAART Era.

Objective: AIDS-related mortality has changed dramatically with the onset of highly active antiretroviral therapy (HAART), which has even allowed compensated HIV-infected patients to withdraw from secondary therapy directed against opportunistic pathogens. However, in recently autopsied HIV-infected patients, we observed that associations with a broad spectrum of pathogens remain, although detailed analyses are lacking. Therefore, we focused on the possible frequency and spectrum shifts in pathogens associated with autopsied HIV-infected patients.

Form of phytosterols and food matrix in which they are incorporated modulate their incorporation into mixed micelles and impact cholesterol micellarization.

Scope: The ability of different plant sterols/stanols (PS) mixtures, which differed in the degree of B-ring saturation and aliphatic side chain structure and saturation, to reduce cholesterol (CH) micellarization was explored.

Methods And Results: Experiments were performed using an in vitro digestion model, synthetic mixed micelles, and pure porcine pancreatic lipases. Sterols were measured by GC-FID.

Systems genetics of metabolism: the use of the BXD murine reference panel for multiscalar integration of traits.

Metabolic homeostasis is achieved by complex molecular and cellular networks that differ significantly among individuals and are difficult to model with genetically engineered lines of mice optimized to study single gene function. Here, we systematically acquired metabolic phenotypes by using the EUMODIC EMPReSS protocols across a large panel of isogenic but diverse strains of mice (BXD type) to study the genetic control of metabolism. We generated and analyzed 140 classical phenotypes and deposited these in an open-access web service for systems genetics (www.

Ppargamma2 is a key driver of longevity in the mouse.

Aging involves a progressive physiological remodeling that is controlled by both genetic and environmental factors. Many of these factors impact also on white adipose tissue (WAT), which has been shown to be a determinant of lifespan. Interrogating a transcriptional network for predicted causal regulatory interactions in a collection of mouse WAT from F2 crosses with a seed set of 60 known longevity genes, we identified a novel transcriptional subnetwork of 742 genes which represent thus-far-unknown longevity genes.

Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics.

Hypertension is a major health problem of largely unknown genetic origins. To identify new genes responsible for hypertension, genetic analysis of recombinant inbred strains of mice followed by human association studies might prove powerful and was exploited in our current study. Using a set of 27 recombinant BXD strains of mice we identified a quantitative trait locus (QTL) for blood pressure (BP) on distal chromosome 9.

The Pro12Ala PPARgamma2 variant determines metabolism at the gene-environment interface.

The metabolic impact of the common peroxisome proliferator-activated receptor gamma isoform 2 (PPARgamma2) variant Pro12Ala in human populations has been widely debated. We demonstrate, using a Pro12Ala knockin model, that on chow diet, Ala/Ala mice are leaner, have improved insulin sensitivity and plasma lipid profiles, and have longer lifespans. Gene-environment interactions played a key role as high-fat feeding eliminated the beneficial effects of the Pro12Ala variant on adiposity, plasma lipids, and insulin sensitivity.

Visceral obesity is associated with high levels of serum squalene.

Objective: To investigate the impact of visceral obesity on cholesterol metabolism in normoglycemic offspring of patients with type 2 diabetes.

Research Methods And Procedures: The proportion of intra-abdominal fat (IAF) was measured by abdominal computer tomography, and serum cholesterol synthesis and absorption markers were determined by gas-liquid chromatography in 109 normoglycemic offspring of patients with type 2 diabetes. Insulin action was measured with the hyperinsulinemic euglycemic clamp.

Adipose tissue expression of the lipid droplet-associating proteins S3-12 and perilipin is controlled by peroxisome proliferator-activated receptor-gamma.

In a systematic search for peroxisome proliferator-activated receptor-gamma (PPAR-gamma) target genes, we identified S3-12 and perilipin as novel direct PPAR-gamma target genes. Together with adipophilin and tail-interacting protein of 47 kDa, these genes are lipid droplet-associating proteins with distinct expression pattern but overlapping expression in adipose tissue. The expression of S3-12 and perilipin is tightly correlated to the expression and activation of PPAR-gamma in adipocytes, and promoter characterization revealed that the S3-12 and the perilipin promoters contain three and one evolutionarily conserved PPAR response elements, respectively.

Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPAR gamma hypomorphic mice.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor, which controls adipocyte differentiation. We targeted with homologous recombination the PPAR gamma 2-specific exon B, resulting in a white adipose tissue knockdown of PPAR gamma. Although homozygous (PPAR gamma hyp/hyp) mice are born with similar weight as the WT mice, the PPAR gamma hyp/hyp animals become growth retarded and develop severe lipodystrophy and hyperlipidemia.

The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegeneration.

Parkinson's disease (PD) is a severe neurological disorder, characterized by the progressive degeneration of the dopaminergic nigrostriatal pathway and the presence of Lewy bodies (LBs). The discovery of genes responsible for familial forms of the disease has provided insights into its pathogenesis. Mutations in the parkin gene, which encodes an E3 ubiquitin-protein ligase involved in the ubiquitylation and proteasomal degradation of specific protein substrates, have been found in nearly 50% of patients with autosomal-recessive early-onset parkinsonism.

PPARgamma, an X-ceptor for Xs.

Evidence from both human genetic studies and characterization of peroxisome proliferator-activated receptor gamma (PPARgamma) knockout mice suggested that the prime function of PPARgamma is fat formation and that its role in insulin sensitization might be secondary to this function. The thrifty function of PPARgamma was most likely evolutionary beneficial, but might in "times of plenty" contribute to the pathogenesis of disorders, such as obesity, insulin resistance, type 2 diabetes, and hyperlipidemia, often commonly referred to as "syndrome X". This role of PPARgamma in these diseases also questions the eventual therapeutic benefits of pure PPARgamma activation, which is associated with an increase in adipose tissue mass.