leptin and Burns

Obesity has become a world-wide pandemic and is considered a major risk factor for various diseases. Despite this, recent intriguing clinical observations have been made suggesting that being overweight has some advantages. Overweight and some obese patients were reported to have significantly lower all-cause mortality, described as the 'obesity paradox'. This phenomenon resulted in increased research aimed at investigating the influence of adipose tissue on outcomes of various clinical states including critical illness. In this review, we summarise research findings on the effect burn injury and trauma-related critical illness have on adipose tissue and discuss potential mechanisms by which adipose tissue influences outcomes in burn and other critically ill patients. Burn injury and critical illness influence adipose tissue functionally and morphologically, with circulating levels of fat derived hormones, adipokines, altered in patients following injury and/or critical illness. As adipokines regulate a variety of processes including inflammation and metabolism, this disruption in the adipokine axis may explain the obesity paradox phenomenon observed in critically ill patients. We conclude that further research on the influence of individual adipokines on prognosis in burn and critically ill patients and the mechanisms involved is required to increase understanding of their therapeutic potential.

Topics: Adipokines; Adiponectin; Adipose Tissue; Burns; Critical Illness; Fibrosis; Ghrelin; Humans; Inflammation; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Overweight; Resistin; Skin; Wound Healing

Both overnutrition and undernutrition affect energy metabolism, with overnutrition raising energy expenditure and undernutrition lowering it. Fever is a powerful stimulator of thermogenesis. In diseases such as cancer, AIDS, diabetes mellitus, and rheumatoid arthritis, whether energy expenditure is increased or decreased often depends on how advanced the disorder is. Early on, when the greater protein turnover characteristic of these conditions is paramount, energy expenditure is increased. In addition, in diseases such as cancer, AIDS, and rheumatoid arthritis in which cytokines are released, the cytokines' thermogenic effect initially increases the metabolic rate. However, as the disease becomes more advanced and leads to cachexia, energy expenditure drops below normal. Acute conditions such as burns and trauma significantly raise energy expenditure, primarily by increasing sympathetic response and the release of catecholamines, which are powerful stimulators of energy expenditure.

Topics: Acquired Immunodeficiency Syndrome; Adult; Age Factors; Aged; Arthritis, Rheumatoid; Basal Metabolism; Burns; Diabetes Mellitus; Eating; Energy Metabolism; Female; Humans; Leptin; Male; Middle Aged; Neoplasms; Obesity; Wounds and Injuries

In current intensive care treatment, some patients with severe burns cannot be saved due to progressive organ failure. Further investigation of the pathogenesis of severe burns is needed to improve the mortality rate. In burns, inflammatory cytokines form a network that leads to an inflammatory response. Adipocytes secrete physiologically active substances (adipokines). The roles of adipokines have not been completely clarified in burn patients. This study aimed to determine the relation between serial changes of adipokines and clinical course in severely burned patients.. This was a single-center, retrospective, observational study. Patients' blood samples were collected on the day of injury and around 1 week later. Adipokines (adiponectin, angiotensinogen, chemerin, CXCL-12/SDF-1, leptin, resistin, vaspin, visfatin), various inflammatory cytokines, syndecan-1 and C1 esterase inhibitor were measured.. Thirty-eight patients were included. Resistin levels were significantly higher in the non-survivors versus survivors on Day 1 after burn injury. Hierarchical clustering analysis showed common clusters on Day 1 and at 1 Week after burn injury (resistin, IL-6, IL-8, IL10 and MCP-1). The correlation coefficient of resistin to SOFA score at 1 Week was significant. Logistic regression analysis showed a significant relation of resistin levels on Day 1 with prognosis; the area under the ROC curve for resistin was 0.801.. In the acute phase of burns, resistin was associated with other pro-inflammatory cytokines and was related to the severity and prognosis of major burns.

Topics: Adipokines; Adiponectin; Angiotensinogen; Burns; Complement C1 Inhibitor Protein; Cytokines; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Leptin; Nicotinamide Phosphoribosyltransferase; Prognosis; Resistin; Retrospective Studies; Syndecan-1

Burn injury is a pathology underpinned by progressive and aberrant inflammation. It is a major clinical challenge to survival and quality of life. Although the complex local and disseminating pathological processes of a burn injury ultimately stem from local tissue damage, to date relatively few studies have attempted to characterise the local inflammatory mediator profile. Here, cytokine content and associated transcriptional changes were measured in rat skin for three hours immediately following induction of a scald-type (60°C, 2 min) burn injury model. Leptin (

Topics: Animals; Burns; Chemokine CX3CL1; Gene Expression Regulation; Janus Kinases; Leptin; Male; Protein Interaction Maps; Rats, Sprague-Dawley; Signal Transduction; Skin; STAT Transcription Factors

Gastrointestinal hormones are essential in postburn metabolism. Since near 50% of burn victims test positive for blood alcohol levels at hospital admission and have inferior outcomes compared to nonintoxicated burn patients; we hypothesized that the gastrointestinal hormone secretion is compromised in intoxicated burn victims. To test our theory, we quantified gastrointestinal hormones serum levels in a combine ethanol intoxication and burn injury mouse model. Thus, mice received a daily dose of ethanol for 3 days, rested 4 days, and were given ethanol 3 additional days. Mice underwent 15% TBSA scald burn 30 minutes after their last ethanol dose. Serum samples were collected 24 hours after burn injury. Nonintoxicated burned mice exhibited an increase in glucose, insulin, ghrelin, plasminogen activator inhibitor-1, leptin, and resistin by 1.4-, 3-, 13.5-, 6.2-, 9.4-, and 2.4-fold, respectively, compared to sham vehicle mice (P < .05). Burn injury also reduced serum gastric inhibitory polypeptide (GIP) by 32% compared to sham-injured, vehicle-treated mice. Leptin, resistin, glucagon-like peptide-1, as well as insulin, were not different from sham groups when intoxication preceded burn injury. Nevertheless, in burned mice treated with ethanol, gastric inhibitory polypeptide and glucagon serum levels exhibited a significant fold increase of 3.5 and 4.7, respectively. With these results, we conclude that 24 hours after burn injury, mice developed significant changes in gastrointestinal hormones, along with hyperglycemia. Moreover, the combined insult of burn and ethanol intoxication led to additional hormonal changes that may be attributed to a potential pancreatic dysfunction. Further multiday studies are required to investigate the etiology, behavior, and clinical significance of these hormonal changes.

Topics: Alcoholic Intoxication; Animals; Blood Glucose; Burns; Ethanol; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Insulin; Leptin; Mice, Inbred C57BL; Models, Animal; Plasminogen Activator Inhibitor 1; Resistin

Hypermetabolism is universal in the severely burned and is characterized by catabolism of lean mass and body fat with associated insulin resistance. Adipokines are likely to play a role in these changes but have not been identified to date in burn patients.. From a single burn ICU, 17 burn patients with an expected stay>14 days were studied. Study period began within 14 days of admission. Over 7 days, plasma samples were collected for measurement of leptin, adiponectin, resistin, ghrelin, insulin, and cortisol by ELISA. For comparison, samples from 15 healthy controls of similar age, BMI, and blood glucose were obtained.. Mean age was 33±17 years and BMI 26±3.4. Average burn size was 45±20% TBSA and ISS 32±10 with 72% having inhalation injury; in-hospital mortality was 29%. Estimated energy needs were 3626±710 kcal, of which 84±21% were met by enteral feeding with intensive insulin treatment (glucose 80-110 mg/ml). Using the homeostasis model assessment of insulin resistance, burned subjects were more resistant than controls (17±11.3 and 8±10.0). Insulin levels were elevated (57±35.6 μU/ml in burned subject vs. 26±31.1 μU/ml in controls), and cortisol concentrations increased (50±41.2 μg/dl vs. 12±3.9 μg/dl). These traditional hormone changes were associated with increased resistin (16.6±5.5 ng/ml vs. 3.8±0.9 ng/ml) and decreased leptin (8.8±8.9 ng/ml vs. 19.4±23.5 ng/ml), adiponectin (9±3.5 ng/ml vs. 17±10.2 ng/ml), and ghrelin (0.37±0.14 ng/ml vs.0.56±0.26 ng/ml).. Patients with burns, who are characteristically hypermetabolic with hypercortisolism and insulin resistant, have significant changes in adipokine levels that appear independent of the magnitude of initial injury or metabolic derangement. In addition, suppression of ghrelin in the presence of decreased leptin and adiponectin levels in combination with increased insulin and resistin levels represent unexpected changes in the metabolic milieu of the injured patient possibly due to dramatic activation of inflammatory pathways, indicating strategies for treatment.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; Body Mass Index; Burns; Female; Ghrelin; Humans; Hydrocortisone; Insulin; Insulin Resistance; Leptin; Male; Resistin

To investigate the effect of topical application of leptin in promoting burn wound healing in rats.. Four parallel second-degree burn wounds induced on the back of 18 Wistar rats were divided into leptin treatment group (treated with topical application of 400 ng/ml leptin dissolved in PBS) and control group (treated with PBS). The time of wound healing was recorded, and the wound area that was not healed was measured at 3, 7, 11, 15, and 19 days after burns. The tissue at the peripheries of the wound was sampled at 7, 14 and 21 days after burns for pathological examination with HE staining and immunohistochemistry for proliferating cell nuclear antigen (PCNA) to evaluate the proliferation of keratinocytes.. Compared with the control group, leptin-treated wounds showed a shorter time (by 2-3 days) of wound healing, and significant differences were found between the two groups in healing at 7, 11, 15, and 19 days after burns. HE staining and immunohistochemistry revealed a faster rate of epidermis growth and a greater thickness of the cuticular layer in leptin-treated wounds at 7, 14 and 21 days after burns. PCNA positivity in the keratinocytes was stronger in leptin-treated wounds than in the control wounds at 7 and 14 days, but no such distinct difference was noted at 21 days between the two groups.. Topical application of leptin can promote re-epithelization in burn wounds to shorten the wound healing time of burns.

Topics: Administration, Cutaneous; Animals; Burns; Leptin; Male; Rats; Rats, Wistar; Wound Healing

Although zinc status is an important parameter in insulin sensitivity, data concerning its implication in noxious burn-induced insulin resistance are scarce. The present study was designed to evaluate the impact of zinc status before burn on the recovery of injury with focus on plasma insulin and glucose levels. The experiment was performed in male adult Wistar rats fed from weaning with a zinc normal diet (80 ppm) or a depleted zinc diet (10 ppm) for 8 weeks and burned to third degree on 20% of their total body surface area. Blood and tissue samples were collected 3, 6, and 24 h after injury in order to study biochemical parameters and the glucose/insulin response in relation with the zinc status. After burn, zinc-depleted rats presented an exacerbated decrease in plasma zinc level. In addition, the burn-induced insulin resistance, leading to protein catabolism, was emphasized, with higher plasma insulin, glucose, and leptin levels in zinc-deficient animals versus normal-fed rats. Our experimental results underlined the interest to early control the zinc status in order to limit the deleterious effects of oxidative stress and insulin resistance in burned patients.

Topics: Animals; Antioxidants; Blood Glucose; Burns; Corticosterone; Diet; Disease Models, Animal; Femur; Insulin; Insulin Resistance; Leptin; Liver; Male; Muscles; Random Allocation; Rats; Rats, Wistar; Zinc

The present study was designed to determine whether exogenous leptin reduces remote organ injury in the rats with thermal burn trauma. Leptin (10 microg/kg) or saline was administered intraperitoneally after burn injury, and the rats were decapitated at either 6 or 24 h. Plasma samples of 24-h burn group were assayed for the determination of monocyte and neutrophil apoptosis. Thermal injury increased tissue-associated myeloperoxidase (MPO) activity and microscopic damage scores in the lung, liver, stomach, colon and kidney of both 6- and 24-h burn groups. In the 6-h burn group, leptin reduced microscopic damage score in the liver and kidney only, while damage scores in the 24-h burn group were reduced in all the tissues except the lung. Also, in both burn groups, leptin reduced elevated MPO activity in all tissues except the lung. The percentage of mononuclear cells was significantly reduced at the 24 h of burn injury, while the granulocyte percentage was increased. Leptin treatment, however, had no significant effect on burn-induced reversal of white blood cell ratios. On the other hand, burn-induced increase in the death of mononuclear cells and granulocytes was significantly reduced in leptin-treated rats. The results of the present study suggest that leptin may provide a therapeutic benefit in diminishing burn-induced inflammation and associated multiple organ failure.

Topics: Animals; Apoptosis; Burns; Flow Cytometry; Granulocytes; Immune System; Inflammation; Kidney; Leptin; Leukocytes; Leukocytes, Mononuclear; Liver; Monocytes; Neutrophils; Peroxidase; Rats; Rats, Sprague-Dawley; Time Factors; Tissue Distribution

The purpose of this study was to investigate the relationship between the plasma leptin level and clinical parameters in patients with burn injury. Six patients with burn injury were admitted to the Emergency and Critical Care Medicine Center of St. Marianna University Hospital within 1h after injury. Plasma levels were monitored for leptin, proinflammatory cytokines (interleukin (IL)-1 beta, IL-6, tumor necrosis factor alpha (TNF alpha)), stress-related parameters (adrenocorticotropic hormone (ACTH), cortisol, and C-reactive protein (CRP)). The change in individual plasma leptin levels did not show similar pattern in all these patients. However, leptin levels remained within the normal range, except in a patient (Case 1) complicated with severe hypovolemic shock. Plasma ACTH and cortisol levels were also elevated in most of the patients. Examination of relationships among plasma leptin, proinflammatory cytokines, and stress-related parameters revealed a significant positive correlation between the plasma leptin level and IL-1 beta or IL-6. These results suggest that the plasma leptin level may have some relations to plasma proinflammatory cytokines in pathophysiologic responses to critical conditions of burn injury.

Topics: Acute Disease; Adrenocorticotropic Hormone; Adult; Aged; Burns; C-Reactive Protein; Cytokines; Female; Humans; Hydrocortisone; Interleukin-1; Interleukin-6; Leptin; Male; Middle Aged; Shock; Time Factors; Tumor Necrosis Factor-alpha