Body composition and body fat distribution in tissue-specific insulin resistance and in response to a 12-week isocaloric dietary macronutrient intervention.

Background: Body composition and body fat distribution are important predictors of cardiometabolic diseases. The etiology of cardiometabolic diseases is heterogenous, and partly driven by inter-individual differences in tissue-specific insulin sensitivity.

Objectives: To investigate (1) the associations between body composition and whole-body, liver and muscle insulin sensitivity, and (2) changes in body composition and insulin sensitivity and their relationship after a 12-week isocaloric diet high in mono-unsaturated fatty acids (HMUFA) or a low-fat, high-protein, high-fiber (LFHP) diet.

The individual response to antibiotics and diet - insights into gut microbial resilience and host metabolism.

Antibiotic use disrupts microbial composition and activity in humans, but whether this disruption in turn affects host metabolic health is unclear. Cohort studies show associations between antibiotic use and an increased risk of developing obesity and type 2 diabetes mellitus. Here, we review available clinical trials and show the disruptive effect of antibiotic use on the gut microbiome in humans, as well as its impact on bile acid metabolism and microbial metabolites such as short-chain fatty acids.

Metabolic phenotyping in people living with obesity: Implications for dietary prevention.

Given the increasing number of people living with obesity and related chronic metabolic disease, precision nutrition approaches are required to increase the effectiveness of prevention strategies. This review addresses these approaches in different metabolic phenotypes (metabotypes) in obesity. Although obesity is typically associated with an increased cardiometabolic disease risk, some people with obesity are relatively protected against the detrimental effects of excess adiposity on cardiometabolic health, also referred to as 'metabolically healthy obesity' (MHO).

Dietary macronutrients and the gut microbiome: a precision nutrition approach to improve cardiometabolic health.

Accumulating evidence indicates that the gut microbiome is an important regulator of body weight, glucose and lipid metabolism, and inflammatory processes, and may thereby play a key role in the aetiology of obesity, insulin resistance and type 2 diabetes. Interindividual responsiveness to specific dietary interventions may be partially determined by differences in baseline gut microbiota composition and functionality between individuals with distinct metabolic phenotypes. However, the relationship between an individual's diet, gut microbiome and host metabolic phenotype is multidirectional and complex, yielding a challenge for practical implementation of targeted dietary guidelines.

The Effect of Vitamin D Supplementation on Insulin Sensitivity: A Systematic Review and Meta-analysis.

Background: Vitamin D has been suggested to affect peripheral insulin sensitivity. Evidence regarding the effect of vitamin D supplementation on insulin sensitivity is still conflicting.

Purpose: This meta-analysis aimed to assess the effect of vitamin D supplementation on insulin sensitivity in humans with or at risk for insulin resistance.

The association between vitamin D receptor polymorphisms and tissue-specific insulin resistance in human obesity.

Background/objectives: To investigate (1) the association of four VDR polymorphisms (TaqI/rs731236, ApaI/rs7975232, FokI/rs10735810, and Bsml/rs1544410) with markers of adiposity and tissue-specific insulin resistance at baseline, after weight loss and weight maintenance; (2) the effect of the VDR polymorphisms in the SAT transcriptome in overweight/obese Caucasians of the DiOGenes cohort.

Methods: We included 553 adult obese individuals (mean BMI 34.8 kg/m), men (n = 197) and women (n = 356) at baseline, following an 8-week weight loss intervention and 26 weeks weight maintenance.

Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans.

Aims/hypothesis: Insulin resistance in skeletal muscle and liver plays a major role in the pathophysiology of type 2 diabetes. The hyperinsulinaemic-euglycaemic clamp is considered the gold standard for assessing peripheral and hepatic insulin sensitivity, yet it is a costly and labour-intensive procedure. Therefore, easy-to-measure, cost-effective approaches to determine insulin sensitivity are needed to enable organ-specific interventions.

Subcutaneous Adipose Tissue and Systemic Inflammation Are Associated With Peripheral but Not Hepatic Insulin Resistance in Humans.

Obesity-related insulin resistance (IR) may develop in multiple organs, representing various etiologies for cardiometabolic diseases. We identified abdominal subcutaneous adipose tissue (ScAT) transcriptome profiles in liver or muscle IR by means of RNA sequencing in overweight or obese participants of the Diet, Obesity, and Genes (DiOGenes) (NCT00390637, ClinicalTrials.gov) cohort ( = 368).

Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans.

Microbial-derived short-chain fatty acids (SCFA) acetate, propionate and butyrate may provide a link between gut microbiota and whole-body insulin sensitivity (IS). In this cross-sectional study (160 participants, 64% male, BMI: 19.2-41.

The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity.

The interplay of gut microbiota, host metabolism, and metabolic health has gained increased attention. Gut microbiota may play a regulatory role in gastrointestinal health, substrate metabolism, and peripheral tissues including adipose tissue, skeletal muscle, liver, and pancreas via its metabolites short-chain fatty acids (SCFA). Animal and human data demonstrated that, in particular, acetate beneficially affects host energy and substrate metabolism via secretion of the gut hormones like glucagon-like peptide-1 and peptide YY, which, thereby, affects appetite, via a reduction in whole-body lipolysis, systemic pro-inflammatory cytokine levels, and via an increase in energy expenditure and fat oxidation.

Adrenergically and non-adrenergically mediated human adipose tissue lipolysis during acute exercise and exercise training.

Obesity-related adipose tissue (AT) dysfunction, in particular subcutaneous AT (SCAT) lipolysis, is characterized by catecholamine resistance and impaired atrial natriuretic peptide (ANP) responsiveness. It remains unknown whether exercise training improves (non-)adrenergically mediated lipolysis in metabolically compromised conditions. We investigated the effects of local combined α-/β-adrenoceptor blockade on abdominal SCAT lipolysis in lean insulin sensitive (IS) (=10), obese IS (=10), and obese insulin resistant (IR) (=10) men.

The effects of angiotensin receptor neprilysin inhibition by sacubitril/valsartan on adipose tissue transcriptome and protein expression in obese hypertensive patients.

Increased activation of the renin-angiotensin system is involved in the onset and progression of cardiometabolic diseases, while natriuretic peptides (NP) may exert protective effects. We have recently demonstrated that sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, which blocks the angiotensin II type-1 receptor and augments natriuretic peptide levels, improved peripheral insulin sensitivity in obese hypertensive patients. Here, we investigated the effects of sacubitril/valsartan (400 mg QD) treatment for 8 weeks on the abdominal subcutaneous adipose tissue (AT) phenotype compared to the metabolically neutral comparator amlodipine (10 mg QD) in 70 obese hypertensive patients.

Gastrointestinal Transit Time, Glucose Homeostasis and Metabolic Health: Modulation by Dietary Fibers.

Gastrointestinal transit time may be an important determinant of glucose homeostasis and metabolic health through effects on nutrient absorption and microbial composition, among other mechanisms. Modulation of gastrointestinal transit may be one of the mechanisms underlying the beneficial health effects of dietary fibers. These effects include improved glucose homeostasis and a reduced risk of developing metabolic diseases such as obesity and type 2 diabetes mellitus.

Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose.

Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [²H₂]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-(13)C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG.