BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis.

Brown adipose tissue (BAT) is best known for thermogenesis. Rodent studies demonstrated that enhanced BAT thermogenesis is tightly associated with increased energy expenditure, reduced body weight, and improved glucose homeostasis. However, human BAT is protective against type 2 diabetes, independent of body weight.

The SLC25A47 locus controls gluconeogenesis and energy expenditure.

Mitochondria provide essential metabolites and adenosine triphosphate (ATP) for the regulation of energy homeostasis. For instance, liver mitochondria are a vital source of gluconeogenic precursors under a fasted state. However, the regulatory mechanisms at the level of mitochondrial membrane transport are not fully understood.

Lipolysis-derived linoleic acid drives beige fat progenitor cell proliferation.

De novo beige adipocyte biogenesis involves the proliferation of progenitor cells in white adipose tissue (WAT); however, what regulates this process remains unclear. Here, we report that in mouse models but also in human tissues, WAT lipolysis-derived linoleic acid triggers beige progenitor cell proliferation following cold acclimation, β3-adrenoceptor activation, and burn injury. A subset of adipocyte progenitors, as marked by cell surface markers PDGFRα or Sca1 and CD81, harbored cristae-rich mitochondria and actively imported linoleic acid via a fatty acid transporter CD36.

Adipose Tissue Remodeling in Pathophysiology.

Rather than serving as a mere onlooker, adipose tissue is a complex endocrine organ and active participant in disease initiation and progression. Disruptions of biological processes operating within adipose can disturb healthy systemic physiology, the sequelae of which include metabolic disorders such as obesity and type 2 diabetes. A burgeoning interest in the field of adipose research has allowed for the elucidation of regulatory networks underlying both adipose tissue function and dysfunction.

Adipose browning response to burn trauma is impaired with aging.

BACKGROUNDThe incidence of burn injuries in older patients is dramatically increasing as the population of older people grows. Despite the increased demand for elderly burn care, the mechanisms that mediate increased morbidity and mortality in older trauma patients are unknown. We recently showed that a burn injury invokes white adipose tissue browning that leads to a substantially increased hypermetabolic response associated with poor outcomes.

Detouring adrenergic stimulation to induce adipose thermogenesis.

Harnessing the thermogenic, energy-expending capacity of adipocytes has the potential to combat metabolic disorders. Although β-adrenergic receptor agonists are the best-known activators of thermogenesis, they carry considerable cardiovascular risks. A new study demonstrates the ability of G protein-coupled receptor 3 to intrinsically drive adipose thermogenesis independent of β-adrenergic receptor signalling.

Adipose-specific ATGL ablation reduces burn injury-induced metabolic derangements in mice.

Hypermetabolism following severe burn injuries is associated with adipocyte dysfunction, elevated beige adipocyte formation, and increased energy expenditure. The resulting catabolism of adipose leads to detrimental sequelae such as fatty liver, increased risk of infections, sepsis, and even death. While the phenomenon of pathological white adipose tissue (WAT) browning is well-documented in cachexia and burn models, the molecular mechanisms are essentially unknown.

Burn-induced hypermetabolism and skeletal muscle dysfunction.

Critical illnesses, including sepsis, cancer cachexia, and burn injury, invoke a milieu of systemic metabolic and inflammatory derangements that ultimately results in increased energy expenditure leading to fat and lean mass catabolism. Burn injuries present a unique clinical challenge given the magnitude and duration of the hypermetabolic response compared with other forms of critical illness, which drastically increase the risk of morbidity and mortality. Skeletal muscle metabolism is particularly altered as a consequence of burn-induced hypermetabolism, as it primarily provides a main source of fuel in support of wound healing.

Interleukin-6 blockade, a potential adjunct therapy for post-burn hypermetabolism.

Severe burns remain a leading cause of death and disability worldwide. Despite advances in patient care, the excessive and uncontrolled hypermetabolic stress response induced by this trauma inevitably affects every organ system causing substantial morbidity and mortality. Recent evidence suggests interleukin-6 (IL-6) is a major culprit underlying post-burn hypermetabolism.

Beyond mitochondria: Alternative energy-producing pathways from all strata of life.

It is well-established that mitochondria are the powerhouses of the cell, producing adenosine triphosphate (ATP), the universal energy currency. However, the most significant strengths of the electron transport chain (ETC), its intricacy and efficiency, are also its greatest downfalls. A reliance on metal complexes (FeS clusters, hemes), lipid moities such as cardiolipin, and cofactors including alpha-lipoic acid and quinones render oxidative phosphorylation vulnerable to environmental toxins, intracellular reactive oxygen species (ROS) and fluctuations in diet.

Biological characteristics of stem cells derived from burned skin-a comparative study with umbilical cord stem cells.

Introduction: Burned human skin, which is routinely excised and discarded, contains viable mesenchymal stromal/stem cells (burn-derived mesenchymal stromal/stem cells; BD-MSCs). These cells show promising potential to enable and aid wound regeneration. However, little is known about their cell characteristics and biological function.

Thermal Stress Induces Long-Term Remodeling of Adipose Tissue and Is Associated with Systemic Dysfunction.

Severe burns are characterized by the magnitude and duration of the hypermetabolic response thereafter, and demarcated by the loss of lean body mass and catabolism of fat stores. The aim of the present study was to delineate the temporal and location-specific physiological changes to adipose depots and downstream consequences post-burn in a murine model of thermal injury. C57BL/6 mice were subjected to a 30% total body surface area burn and body mass, food intake, and tissue mass were monitored for various time points up until 60 days postinjury.

Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells-a paradigm change.

Background: Multipotent mesenchymal stromal/stem cell (MSC) therapy is under investigation in promising (pre-)clinical trials for wound healing, which is crucial for survival; however, the optimal cell dosage remains unknown. The aim was to investigate the efficacy of different low-to-high MSC dosages incorporated in a biodegradable collagen-based dermal regeneration template (DRT) Integra®.

Methods: We conducted a porcine study (N = 8 Yorkshire pigs) and seeded between 200 and 2,000,000 cells/cm of umbilical cord mesenchymal stromal/stem cells on the DRT and grafted it onto full-thickness burn excised wounds.

Adipose Tissue Metabolic Function and Dysfunction: Impact of Burn Injury.

For decades, adipose tissue had been considered as merely a storage depot and cushion to protect organs against trauma and injury. However, in recent years, a number of impactful studies have pinpointed the adipose tissue as an endocrine organ mediating systemic dysfunction in not only metabolic disorders such as obesity, but also in the stages following traumatic events such as severe burns. For instance, thermal injury induces a chronic β-adrenergic response associated with drastic increases in adipose lipolysis, macrophage infiltration and IL-6 mediated browning of white adipose tissue (WAT).

Regulation of glycolysis and the Warburg effect in wound healing.

One of the most significant adverse postburn responses is abnormal scar formation, such as keloids. Despite its prolificacy, the underlying pathophysiology of keloid development is unknown. We recently demonstrated that NLRP3 inflammasome, the master regulator of inflammatory and metabolic responses (e.

Browning of white adipose tissue after a burn injury promotes hepatic steatosis and dysfunction.

Burn patients experiencing hypermetabolism develop hepatic steatosis, which is associated with liver failure and poor outcomes after the injury. These same patients also undergo white adipose tissue (WAT) browning, which has been implicated in mediating post-burn cachexia and sustained hypermetabolism. Despite the clinical presentation of hepatic steatosis and WAT browning in burns, whether or not these two pathological responses are linked remains poorly understood.

Metformin prevents the pathological browning of subcutaneous white adipose tissue.

Objective: Browning, the conversion of white adipose tissue (WAT) to a beige phenotype, has gained interest as a strategy to induce weight loss and improve insulin resistance in metabolic disorders. However, for hypermetabolic conditions stemming from burn trauma or cancer cachexia, browning is thought to contribute to energy wasting and supraphysiological nutritional requirements. Metformin's impact on this phenomenon and underlying mechanisms have not been explored.

Inhibition of Lipolysis With Acipimox Attenuates Postburn White Adipose Tissue Browning and Hepatic Fat Infiltration.

Extensive burn injuries promote an increase in the lipolysis of white adipose tissue (WAT), a complication that enhances postburn hypermetabolism contributing to hyperlipidemia and hepatic steatosis. The systemic increase of free fatty acids (FFAs) due to burn-induced lipolysis and subsequent organ fatty infiltration may culminate in multiple organ dysfunction and, ultimately, death. Thus, reducing WAT lipolysis to diminish the mobilization of FFAs may render an effective means to improve outcomes postburn.

Catecholamines Induce Endoplasmic Reticulum Stress Via Both Alpha and Beta Receptors.

Severely burned patients suffer from a hypermetabolic syndrome that can last for years after the injury has resolved. The underlying cause of these metabolic alterations most likely involves the persistent elevated catecholamine levels that follow the surge induced by thermal injury. At the cellular level, endoplasmic reticulum (ER) stress in metabolic tissues is a hallmark observed in patients following burn injury and is associated with several detrimental effects.

Hepatic steatosis associated with decreased β-oxidation and mitochondrial function contributes to cell damage in obese mice after thermal injury.

Severely burned patients who are morbidly obese have poor clinical outcomes with aggravated metabolic consequences, a higher incidence of multiple organ dysfunction/failure, and significantly increased morbidity and mortality. The underlying mechanisms of these adverse outcomes are essentially unknown. Since the liver is one of the central metabolic organs, we hypothesized that thermal injury in obese patients leads to substantially increased lipolysis, hepatic fat infiltration, resulting in profound hepatic cellular and organellar alterations, consequently causing liver damage and severely augmented metabolic dysfunction.