Insights into the neurobiology of weight loss after bariatric surgery and GLP-1R agonists.

Obesity and its related complications are growing in prevalence worldwide, with increasing impact to individuals and healthcare systems alike. Currently, the leading treatment approaches for effective and sustained weight loss are bariatric surgery and gut peptide therapeutics. At a high level, both treatment strategies work by hijacking gut-brain axis signaling to reduce food intake.

Validation of a Food Frequency Questionnaire: VioScreen-Allergy.

Background/objectives: An adapted version of an online pictorial food frequency questionnaire (FFQ), VioScreen-Allergy, assesses total dietary intake and intake of allergens and foods in the maternal diet index (MDI), linked to offspring allergy. This study assessed intermethod reliability, test-retest reliability, and external validity of the VioScreen-Allergy.

Methods: Females of childbearing age were recruited at Denver Health and Children's Hospital, Colorado, USA, and were asked to complete four 24 h recalls and two VioScreen-Allergy FFQs over the course of a month.

Metabolic effects of an essential amino acid supplement in adolescents with PCOS and obesity.

Objective: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, insulin resistance, and hepatic steatosis (HS). Because dietary essential amino acid (EAA) supplementation has been shown to decrease HS in various populations, this study's objective was to determine whether supplementation would decrease HS in PCOS.

Methods: A randomized, double-blind, crossover, placebo-controlled trial was conducted in 21 adolescents with PCOS (BMI 37.

Intestinal epithelial adaptations to vertical sleeve gastrectomy defined at single-cell resolution.

The gut plays a key role in regulating metabolic health. Dietary factors disrupt intestinal physiology and contribute to obesity and diabetes, whereas bariatric procedures such as vertical sleeve gastrectomy (VSG) cause gut adaptations that induce robust metabolic improvements. However, our understanding of these adaptations at the cellular and molecular levels remains limited.

Plasma undercarboxylated osteocalcin dynamics with glycemic stress reflects insulin sensitivity and beta-cell function in humans with and without T2DM.

This study aimed to better understand the relationship between bone-related biomarkers and nutrient stress in the context of metabolic health. We investigated plasma osteocalcin (OC) during an oral glucose challenge and experimental hyperinsulinemia in Type 2 diabetes (T2DM) and lean healthy controls (LHC). Older individuals with obesity and T2DM (n = 9) and young LHCs (n = 9) underwent a 75g oral glucose tolerance test (OGTT) and a 40 mU/m/min hyperinsulinemic-euglycemic clamp.

Soluble RAGE and skeletal muscle tissue RAGE expression profiles in lean and obese young adults across differential aerobic exercise intensities.

Nearly 40% of Americans have obesity and are at increased risk for developing type 2 diabetes. Skeletal muscle is responsible for >80% of insulin-stimulated glucose uptake that is attenuated by the inflammatory milieu of obesity and augmented by aerobic exercise. The receptor for advanced glycation endproducts (RAGE) is an inflammatory receptor directly linking metabolic dysfunction with inflammation.

Pre- and Post-Sexual Maturity Liver-specific ERα Knockout Does Not Impact Hepatic Mitochondrial Function.

Compared with males, premenopausal women and female rodents are protected against hepatic steatosis and present with higher functioning mitochondria (greater hepatic mitochondrial respiration and reduced HO emission). Despite evidence that estrogen action mediates female protection against steatosis, mechanisms remain unknown. Here we validated a mouse model with inducible reduction of liver estrogen receptor alpha (ERα) (LERKO) via adeno-associated virus (AAV) Cre.

Oral combined contraceptives induce liver mitochondrial reactive oxygen species and whole-body metabolic adaptations in female mice.

Compared to age-matched men, pre-menopausal women show greater resilience against cardiovascular disease (CVD), hepatic steatosis, diabetes and obesity - findings that are widely attributed to oestrogen. However, meta-analysis data suggest that current use of oral combined contraceptives (OC) is a risk factor for myocardial infarction, and OC use further compounds with metabolic disease risk factors to increase CVD susceptibility. While mitochondrial function in tissues such as the liver and skeletal muscle is an emerging mechanism by which oestrogen may confer its protection, effects of OC use on mitochondria and metabolism in the context of disease risk remain unexplored.

Exercise reduces the protein abundance of TXNIP and its interacting partner REDD1 in skeletal muscle: potential role for a PKA-mediated mechanism.

Thioredoxin-interacting protein (TXNIP) negatively effects the redox state and growth signaling via its interactions with thioredoxin (TRX) and regulated in development and DNA damage response 1 (REDD1), respectively. TXNIP expression is downregulated by pathways activated during aerobic exercise (AE), via posttranslational modifications (PTMs; serine phosphorylation and ubiquitination). The purpose of this investigation was to determine the effects of acute AE on TXNIP expression, posttranslational modifications, and its interacting partners, REDD1 and TRX.

Advanced Glycation End Products and Inflammatory Cytokine Profiles in Maintenance Hemodialysis Patients After the Ingestion of a Protein-Dense Meal.

Objective: The goal of this investigation was to evaluate circulating and skeletal muscle inflammatory biomarkers between maintenance hemodialysis (MHD) and demographic-matched control subjects (CON) before and after ingestion of a protein-rich meal.

Design And Methods: CON (n = 8; 50 ± 2 years; 31 ± 1 kg/m) and MHD patients (n = 8; 56 ± 5 years; 32 ± 2 kg/m) underwent a basal blood draw and muscle biopsy and serial blood draws after the ingestion of a mixed meal on a nondialysis day. Plasma advanced glycation end products (AGEs) and markers of oxidation were assessed via liquid chromatography-tandem mass spectrometry before and after the meal (+240 min).

Mild Cognitive Impairment and Donepezil Impact Mitochondrial Respiratory Capacity in Skeletal Muscle.

Alzheimer's Disease (ad) associates with insulin resistance and low aerobic capacity, suggestive of impaired skeletal muscle mitochondrial function. However, this has not been directly measured in AD. This study (   = 50) compared muscle mitochondrial respiratory function and gene expression profiling in cognitively healthy older adults (CH;  = 24) to 26 individuals in the earliest phase of ad-related cognitive decline, mild cognitive impairment (MCI;   = 11) or MCI taking the ad medication donepezil (MCI + med;   = 15).

Estradiol treatment or modest exercise improves hepatic health and mitochondrial outcomes in female mice following ovariectomy.

We recently reported that compared with males, female mice have increased hepatic mitochondrial respiratory capacity and are protected against high-fat diet-induced steatosis. Here, we sought to determine the role of estrogen in hepatic mitochondrial function, steatosis, and bile acid metabolism in female mice and investigate potential benefits of exercise in the absence or presence of estrogen via ovariectomy (OVX). Female C57BL mice ( = 6 per group) were randomly assigned to sham surgery (sham), ovariectomy (OVX), or OVX plus estradiol replacement therapy (OVX + Est).

Heat Treatment Improves Hepatic Mitochondrial Respiratory Efficiency via Mitochondrial Remodeling.

Nonacholic fatty liver disease, or hepatic steatosis, is the most common liver disorder affecting the western world and currently has no pharmacologic cure. Thus, many investigations have focused on alternative strategies to treat or prevent hepatic steatosis. Our laboratory has shown that chronic heat treatment (HT) mitigates glucose intolerance, insulin resistance, and hepatic steatosis in rodent models of obesity.

Barriers in translating preclinical rodent exercise metabolism findings to human health.

Physical inactivity and low aerobic capacity are primary drivers of chronic disease pathophysiology and are independently associated with all-cause mortality. Conversely, increased physical activity and exercise are central to metabolic disease prevention and longevity. Although these relationships are well characterized in the literature, what remains incompletely understood are the mechanisms by which physical activity/exercise prevents disease.

Sex and BNIP3 genotype, rather than acute lipid injection, modulate hepatic mitochondrial function and steatosis risk in mice.

Both lipid oversupply and poor mitochondrial function (low respiration and elevated HO emission) have been implicated in the development of hepatic steatosis and liver injury. Mitophagy, the targeted degradation of low-functioning mitochondria, is critical for maintaining mitochondrial quality control. Here, we used intralipid injection combined with acute (4 day) and chronic (4-7wk) high-fat diets (HFD) to examine whether hepatic mitochondrial respiration would decrease and HO emission would increase with lipid overload.

Sex modulates hepatic mitochondrial adaptations to high-fat diet and physical activity.

The impact of sexual dimorphism and mitophagy on hepatic mitochondrial adaptations during the treatment of steatosis with physical activity are largely unknown. Here, we tested if deficiencies in liver-specific peroxisome proliferative activated-receptor-γ coactivator-1α (PGC-1α), a transcriptional coactivator of biogenesis, and BCL-2/ADENOVIRUS EIB 19-kDa interacting protein (BNIP3), a mitophagy regulator, would impact hepatic mitochondrial adaptations (respiratory capacity, HO production, mitophagy) to a high-fat diet (HFD) and HFD plus physical activity via voluntary wheel running (VWR) in both sexes. Male and female wild-type (WT), liver-specific PGC-1α heterozygote (LPGC-1α), and BNIP3 null mice were thermoneutral housed (29-31°C) and divided into three groups: sedentary-low-fat diet (LFD), 16 wk of (HFD), or 16 wk of HFD with VWR for the final 8 wk (HFD + VWR) ( = 5-7/sex/group).

Divergent Changes in Plasma AGEs and sRAGE Isoforms Following an Overnight Fast in T1DM.

Advanced glycation end products (AGEs) promote the development of diabetic complications through activation of their receptor (RAGE). Isoforms of soluble RAGE (sRAGE) sequester AGEs and protect against RAGE-mediated diabetic complications. We investigated the effect of an overnight fast on circulating metabolic substrates, hormones, AGEs, and sRAGE isoforms in 26 individuals with type 1 diabetes (T1DM).

A single high-fat meal alters human soluble RAGE profiles and PBMC RAGE expression with no effect of prior aerobic exercise.

A high-fat diet can induce inflammation and metabolic diseases such as diabetes and atherosclerosis. The receptor for advanced glycation endproducts (RAGE) plays a critical role in metabolic disease pathophysiology and the soluble form of the receptor (sRAGE) can mitigate these effects. However, little is known about RAGE in the postprandial condition and the effect of exercise in this context.

Problems Experienced in the First Month After Discharge From a Heart Failure-Related Hospitalization.

Purpose: Heart failure is a global health concern with high morbidity and mortality rates. Individuals with heart failure commonly experience problems that impact daily life. However, little is known regarding which problems are most significant during the immediate posthospitalization period.

Metabolic Derangements Contribute to Reduced sRAGE Isoforms in Subjects with Alzheimer's Disease.

Although there is evidence for metabolic dysfunction and chronic inflammation in Alzheimer's disease (AD), circulating levels of soluble receptor for advanced glycation end products (sRAGE) and the receptor for advanced glycation end products (RAGE) ligand S100B have not been characterized. sRAGE is an important mediator in disease as it can act as a ligand decoy for RAGE and attenuate downstream inflammatory signaling. Cognitively healthy elderly and AD participants with and without type 2 diabetes ( = 135) were stratified according to the clinical dementia rating (CDR; 0 = normal cognition (NC); ≥0.

The effect of category learning on attentional modulation of visual cortex.

Learning about visual object categories causes changes in the way we perceive those objects. One likely mechanism by which this occurs is the application of attention to potentially relevant objects. Here we test the hypothesis that category membership influences the allocation of attention, allowing attention to be applied not only to object features, but to entire categories.

Effect of a single bout of aerobic exercise on high-fat meal-induced inflammation.

Background And Aims: Chronic low-grade inflammation is involved in the development of metabolic disorders including atherosclerosis, type 2 diabetes (T2D) and metabolic syndrome. Aerobic exercise has been shown to be anti-inflammatory and attenuate postprandial blood lipids, however, the effect of exercise on postprandial inflammation remains unclear. The aim of this study was to determine the protective effect of a single bout of aerobic exercise against postprandial lipemia and peripheral blood mononuclear cell (PBMC) inflammation and to evaluate associations with changes in the energy-sensing enzyme, AMP-activated protein kinase (AMPK).

Acceptability of a brief computerized intervention targeting anxiety sensitivity.

Despite the well-documented efficacy of cognitive behavioral treatments for anxiety disorders, the acceptability of these treatments remains an under-researched area. A better understanding of acceptability could help to improve the initiation of, and engagement in, these effective interventions. Recent research has suggested computerized interventions of anxiety-related risk factors may be one way to improve acceptability and overcome several common barriers to treatment.