The role of tissue oxygenation in obesity-related cardiometabolic complications.

Obesity is a complex, multifactorial, chronic disease that acts as a gateway to a range of other diseases. Evidence from recent studies suggests that changes in oxygen availability in the microenvironment of metabolic organs may exert an important role in the development of obesity-related cardiometabolic complications. In this review, we will first discuss results from observational and controlled laboratory studies that examined the relationship between reduced oxygen availability and obesity-related metabolic derangements.

Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity.

Polyphenols exert beneficial effects on host metabolism, which may be mediated by the gut microbiota. We investigated sex-specific differences in microbiota composition and interactions with cardiometabolic parameters after polyphenol supplementation in individuals with overweight/obesity. In a double-blind, randomized, placebo-controlled trial, 19 women and 18 men with normal glucose tolerance and body mass index >25 kg/m received epigallocatechin-3-gallate and resveratrol (EGCG+RES, 282 + 80 mg/d) or placebo supplements for 12 weeks.

Fas (CD95) expression in adipocytes contributes to diet-induced obesity.

Objective: Induction of browning in white adipose tissue (WAT) increases energy expenditure and may be an attractive target for the treatment of obesity. Since activation of Fas (CD95) induces pathways known to blunt expression of uncoupling protein 1 (UCP1), we hypothesized that Fas expression in adipocytes inhibits WAT browning and thus contributes to the development of obesity.

Methods: Adipocyte-specific Fas knockout (Fas) and control littermate (Fas) mice were fed a regular chow diet or a high-fat diet (HFD) for 20 weeks.

Fasting and postprandial plasma metabolite responses to a 12-wk dietary intervention in tissue-specific insulin resistance: a secondary analysis of the PERSonalized glucose Optimization through Nutritional intervention (PERSON) randomized trial.

Background: We previously showed that dietary intervention effects on cardiometabolic health were driven by tissue-specific insulin resistance (IR) phenotype: individuals with predominant muscle IR (MIR) benefited more from a low-fat, high-protein, and high-fiber (LFHP) diet, whereas individuals with predominant liver insulin resistance (LIR) benefited more from a high-monounsaturated fatty acid (HMUFA) diet.

Objectives: To further characterize the effects of LFHP and HMUFA diets and their interaction with tissue-specific IR, we investigated dietary intervention effects on fasting and postprandial plasma metabolite profile.

Methods: Adults with MIR or LIR (40-75 y, BMI 25-40 kg/m) were randomly assigned to a 12-wk HMUFA or LFHP diet (n = 242).

The impact of duration and severity of obesity exposure on cardiometabolic health.

Purpose: Duration and severity of exposure to excess adipose tissue are important risk factors for complications, but are generally not examined in conjunction. We developed a metric considering both factors to examine the relationship between obesity-related complications and parameters of cardiometabolic health in patients undergoing a metabolic bariatric procedure (MBS).

Materials & Methods: Data from patients screened for primary MBS between 2017 and 2021 were analyzed.

Immunometabolic Signatures of Circulating Monocytes in Humans With Obesity and Insulin Resistance.

Obesity is associated with chronic inflammation and metabolic complications, including insulin resistance (IR). Immune cells drive inflammation through the rewiring of intracellular metabolism. However, the impact of obesity-related IR on the metabolism and functionality of circulating immune cells, like monocytes, remains poorly understood.

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.

Leveraging continuous glucose monitoring for personalized modeling of insulin-regulated glucose metabolism.

Continuous glucose monitoring (CGM) is a promising, minimally invasive alternative to plasma glucose measurements for calibrating physiology-based mathematical models of insulin-regulated glucose metabolism, reducing the reliance on in-clinic measurements. However, the use of CGM glucose, particularly in combination with insulin measurements, to develop personalized models of glucose regulation remains unexplored. Here, we simultaneously measured interstitial glucose concentrations using CGM as well as plasma glucose and insulin concentrations during an oral glucose tolerance test (OGTT) in individuals with overweight or obesity to calibrate personalized models of glucose-insulin dynamics.

Hepatic insulin resistance and muscle insulin resistance are characterized by distinct postprandial plasma metabolite profiles: a cross-sectional study.

Background: Tissue-specific insulin resistance (IR) predominantly in muscle (muscle IR) or liver (liver IR) has previously been linked to distinct fasting metabolite profiles, but postprandial metabolite profiles have not been investigated in tissue-specific IR yet. Given the importance of postprandial metabolic impairments in the pathophysiology of cardiometabolic diseases, we compared postprandial plasma metabolite profiles in response to a high-fat mixed meal between individuals with predominant muscle IR or liver IR.

Methods: This cross-sectional study included data from 214 women and men with BMI 25-40 kg/m, aged 40-75 years, and with predominant muscle IR or liver IR.

Impaired Mitochondrial Respiration in Upper Compared to Lower Body Differentiated Human Adipocytes and Adipose Tissue.

Context: Abdominal obesity is associated with increased cardiometabolic disease risk, while lower body fat seems to confer protection against obesity-related complications. The functional differences between upper and lower body adipose tissue (AT) remain poorly understood.

Objective: We aimed to examine whether mitochondrial respiration is impaired in abdominal as compared to femoral differentiated human multipotent adipose-derived stem cells (hMADS; primary outcome) and AT in postmenopausal women.

Fetuin B in white adipose tissue induces inflammation and is associated with peripheral insulin resistance in mice and humans.

Objective: Fetuin B is a steatosis-responsive hepatokine that causes glucose intolerance in mice, but the underlying mechanisms remain incompletely described. This study aimed to elucidate the mechanisms of action of fetuin B by investigating its putative effects on white adipose tissue metabolism.

Methods: First, fetuin B gene and protein expression was measured in multiple organs in mice and in cultured adipocytes.

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).

Achieving consensus on the language of obesity: a modified Delphi study.

Background: Obesity is recognized by the World Health Organization as a chronic disease. As such, it should be referred to using the language of chronic diseases, with correct and established terminology and definitions. This study was designed to map the current language used to discuss obesity and to compare this with the standard language used for chronic disease.

Quantifying postprandial glucose responses using a hybrid modeling approach: Combining mechanistic and data-driven models in The Maastricht Study.

Computational models of human glucose homeostasis can provide insight into the physiological processes underlying the observed inter-individual variability in glucose regulation. Modelling approaches ranging from "bottom-up" mechanistic models to "top-down" data-driven techniques have been applied to untangle the complex interactions underlying progressive disturbances in glucose homeostasis. While both approaches offer distinct benefits, a combined approach taking the best of both worlds has yet to be explored.

Distinct inflammatory signatures of upper and lower body adipose tissue and adipocytes in women with normal weight or obesity.

Introduction: Upper and lower body fat accumulation poses an opposing obesity-related cardiometabolic disease risk. Depot-differences in subcutaneous adipose tissue (SAT) function may underlie these associations. We aimed to investigate the inflammatory signatures of abdominal (ABD) and femoral (FEM) SAT in postmenopausal women with normal weight or obesity.

The effect of weight loss on whole-body and tissue-specific insulin sensitivity and hepatic lipid content and composition: SWEET substudy.

Objective: This study (1) investigated the effect of weight loss on whole-body and tissue-specific insulin sensitivity and on intrahepatic lipid (IHL) content and composition and (2) investigated the association between weight-loss-induced changes in insulin sensitivity and IHL content in individuals with overweight or obesity.

Methods: In this secondary analysis of the European SWEET project, 50 adults (age 18-65 years) with overweight or obesity (BMI ≥ 25 kg/m ) followed a low-energy diet (LED) for 2 months. At baseline and after the LED, body composition (dual-energy x-ray absorptiometry), IHL content and composition (proton magnetic resonance spectroscopy), whole-body insulin sensitivity (Matsuda index), muscle insulin sensitivity index (MISI), and hepatic insulin resistance index (HIRI) were determined (7-point oral glucose tolerance test).

Circulating and adipose tissue immune cells in tissue-specific insulin resistance in humans with overweight and obesity.

Objective: A proinflammatory adipose tissue (AT) microenvironment and systemic low-grade inflammation may differentially affect tissue-specific insulin sensitivity. This study investigated the relationships of abdominal subcutaneous AT (aSAT) and circulating immune cells, aSAT gene expression, and circulating inflammatory markers with liver and skeletal muscle insulin sensitivity in people with overweight and obesity.

Methods: Individuals with overweight and obesity from the PERSonalized Glucose Optimization Through Nutritional Intervention (PERSON) Study (n = 219) and the Maastricht Study (replication cohort; n = 1256) underwent a seven-point oral glucose tolerance test to assess liver and muscle insulin sensitivity, and circulating inflammatory markers were determined.

The impact of mild hypoxia exposure on myokine secretion in human obesity.

Background/objective: Compelling evidence indicates that myokines act in an autocrine, paracrine and endocrine manner to alter metabolic homeostasis. The mechanisms underlying exercise-induced changes in myokine secretion remain to be elucidated. Since exercise acutely decreases oxygen partial pressure (pO) in skeletal muscle (SM), the present study was designed to test the hypothesis that (1) hypoxia exposure impacts myokine secretion in primary human myotubes and (2) exposure to mild hypoxia in vivo alters fasting and postprandial plasma myokine concentrations in humans.

E-DES-PROT: A novel computational model to describe the effects of amino acids and protein on postprandial glucose and insulin dynamics in humans.

Current computational models of whole-body glucose homeostasis describe physiological processes by which insulin regulates circulating glucose concentrations. While these models perform well in response to oral glucose challenges, interaction with other nutrients that impact postprandial glucose metabolism, such as amino acids (AAs), is not considered. Here, we developed a computational model of the human glucose-insulin system, which incorporates the effects of AAs on insulin secretion and hepatic glucose production.

Physical activity and sedentary behavior show distinct associations with tissue-specific insulin sensitivity in adults with overweight.

Aim: The aim of this study is to investigate associations between the physical activity (PA) spectrum (sedentary behavior to exercise) and tissue-specific insulin resistance (IR).

Methods: We included 219 participants for analysis (median [IQR]: 61 [55; 67] years, BMI 29.6 [26.

Cardiometabolic health improvements upon dietary intervention are driven by tissue-specific insulin resistance phenotype: A precision nutrition trial.

Precision nutrition based on metabolic phenotype may increase the effectiveness of interventions. In this proof-of-concept study, we investigated the effect of modulating dietary macronutrient composition according to muscle insulin-resistant (MIR) or liver insulin-resistant (LIR) phenotypes on cardiometabolic health. Women and men with MIR or LIR (n = 242, body mass index [BMI] 25-40 kg/m, 40-75 years) were randomized to phenotype diet (PhenoDiet) group A or B and followed a 12-week high-monounsaturated fatty acid (HMUFA) diet or low-fat, high-protein, and high-fiber diet (LFHP) (PhenoDiet group A, MIR/HMUFA and LIR/LFHP; PhenoDiet group B, MIR/LFHP and LIR/HMUFA).

Effects of hypoxic exercise on 24-hour glucose profile and substrate metabolism in overweight and obese men with impaired glucose metabolism.

Hypoxic exercise (HE) may have more pronounced effects on glucose homeostasis than exercise under normoxic conditions (NE), but effects on 24-h glucose profile and substrate utilization remain unclear. We investigated the effects of moderate-intensity HE compared with NE on 24-h glucose profile and substrate metabolism in overweight/obese individuals. Ten overweight/obese men with impaired glucose homeostasis participated in a randomized, single-blind, crossover trial.

Physiological Oxygen Levels Differentially Regulate Adipokine Production in Abdominal and Femoral Adipocytes from Individuals with Obesity Versus Normal Weight.

Adipose tissue (AT) inflammation may increase obesity-related cardiometabolic complications. Altered AT oxygen partial pressure (pO) may impact the adipocyte inflammatory phenotype. Here, we investigated the effects of pO levels on the inflammatory phenotype of abdominal (ABD) and femoral (FEM) adipocytes derived from postmenopausal women with normal weight (NW) or obesity (OB).