Levels of β-klotho determine the thermogenic responsiveness of adipose tissues: involvement of the autocrine action of FGF21.

Fibroblast growth factor-21 (FGF21) is a hormonal regulator of metabolism; it promotes glucose oxidation and the thermogenic capacity of adipose tissues. The levels of β-klotho (KLB), the co-receptor required for FGF21 action, are decreased in brown (BAT) and white (WAT) adipose tissues during obesity, diabetes, and lipodystrophy. Reduced β-klotho levels have been proposed to account for FGF21 resistance in these conditions.

Altered GDF15 and FGF21 Levels in Response to Strenuous Exercise: A Study in Marathon Runners.

Background: Recreational marathon runners face strong physiological challenges. Assessment of potential biomarkers for the biological responses of runners will help to discriminate individual race responsiveness and their physiological consequences. This study sought to analyze the changes in the plasma levels of GDF15 and FGF21, novel endocrine factors related to metabolic stress, in runners following the strenuous exercise of a marathon race.

The kallikrein-kinin pathway as a mechanism for auto-control of brown adipose tissue activity.

Brown adipose tissue (BAT) is known to secrete regulatory factors in response to thermogenic stimuli. Components of the BAT secretome may exert local effects that contribute to BAT recruitment and activation. Here, we found that a thermogenic stimulus leads to enhanced secretion of kininogen (Kng) by BAT, owing to induction of kininogen 2 (Kng2) gene expression.

Differential association between S100A4 levels and insulin resistance in prepubertal children and adult subjects with clinically severe obesity.

Objectives: S100A4 has been recently identified as an adipokine associated with insulin resistance (IR) in adult subjects with obesity. However, no data about its levels in children with obesity and only a few approaches regarding its potential mechanism of action have been reported. To obtain a deeper understanding of the role of S100A4 in obesity, (a) S100A4 levels were measured in prepubertal children and adult subjects with and without obesity and studied the relationship with IR and (b) the effects of S100A4 in cultured human adipocytes and vascular smooth muscle cells (VSMCs) were determined.

Glucocorticoid gene regulation of aquaporin-7.

AQP7 is the primary glycerol transporter in white (WAT) and brown (BAT) adipose tissues. There are immediate and quantitatively important actions of cortisone over the expression of AQP7 in murine and human adipocytes. Short-term response (minutes) of cortisone treatment result in an mRNA overexpression in white and brown differentiated adipocytes (between 1.

Circulating growth-and-differentiation factor-15 in early life: relation to prenatal and postnatal growth and adiposity measurements.

Background: Growth-and-differentiation-factor-15 (GDF15) is a regulator of energy homeostasis. To determine the relationship between circulating GDF15 and parameters of metabolic health, we assessed longitudinally GDF15 concentrations in infants born either appropriate- (AGA) or small-for-gestational-age (SGA), the latter population known to be at risk for metabolic alterations, particularly after a rapid postnatal catch-up in weight.

Methods: The study cohort consisted of 103 infants (70 AGA and 33 SGA).

A Role for Oncostatin M in the Impairment of Glucose Homeostasis in Obesity.

Context: Oncostatin M (OSM) plays a key role in inflammation, but its regulation and function during obesity is not fully understood.

Objective: The aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice.

Brown Adipocytes Secrete GDF15 in Response to Thermogenic Activation.

Objective: Transcriptomic analysis of gene expression in brown adipose tissue (BAT) from mice in response to cold revealed strong induction of growth and differentiation factor 15 (GDF15). This study aimed to characterize GDF15 as a brown adipokine released in response to thermogenic activation and to determine its target functions.

Methods: GDF15 expression was measured in adipose tissues from mice in response to physiological and pharmacological modulators of thermogenesis.

GPR120 controls neonatal brown adipose tissue thermogenic induction.

Adaptive induction of thermogenesis in brown adipose tissue (BAT) is essential for the survival of mammals after birth. We show here that G protein-coupled receptor protein 120 (GPR120) expression is dramatically induced after birth in mouse BAT. GPR120 expression in neonatal BAT is the highest among GPR120-expressing tissues in the mouse at any developmental stage tested.

Parkin controls brown adipose tissue plasticity in response to adaptive thermogenesis.

Parkin is an ubiquitin-E3 ligase that acts as a key component of the cellular machinery for mitophagy. We show here that Parkin expression is reciprocally regulated in brown adipose tissue in relation to thermogenic activity. Thermogenic stimuli repress Parkin gene expression via transcriptional mechanisms that are elicited by noradrenergic and PPARα-mediated pathways that involve intracellular lipolysis in brown adipocytes.

GDF-15 Is Elevated in Children with Mitochondrial Diseases and Is Induced by Mitochondrial Dysfunction.

Background: We previously described increased levels of growth and differentiation factor 15 (GDF-15) in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF-21). To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction.