ALCOHOLISM: CLINICAL AND EXPERIMENTAL RESEARCH
Vol. 38, No. 1 January 2014
Alcohol Binging Exacerbates Adipose Tissue Inflammation Following Burn Injury Patricia E. Molina
Background: Alcohol intoxication resulting from binge-drinking episodes is a leading cause of traumatic injury. Alcohol affects systemic responses critical for restoring homeostasis during the postinjury period. The lingering consequences of alcohol intoxication at time of injury are of relevance to the management of the trauma victim. Methods: The study by Qin and colleagues (2013) used intraperitoneal alcohol administration to achieve blood alcohol concentrations of approximately 150 mg/dl to investigate its impact on adipose tissue inflammation following burn injury in a rodent model. The report and the pertinent literature were reviewed to provide perspective on the findings. Results: Their results provide evidence of a marked increase in adipose inflammation during the postburn period. These findings identify a potential mechanism by which alcohol abuse and injury can synergize to promote a dysregulated environment conducive to insulin resistance, hyperglycemia, and potentially metabolic syndrome if the inflammatory changes in adipose tissue observed were to be sustained over prolonged periods. Conclusions: Adipose tissue inflammation potentially leading to metabolic dysregulation during the period following burn injury may further add to the complexities in the management of these patients. The underlying mechanisms need further investigation. The existence of an alcohol use disorder in burn or trauma victims should lead to increased awareness of possible metabolic complications during the recovery period that could be explained by enhanced adipose tissue inflammation. Key Words: Alcohol Binge, Burn Injury, Adipose, Inflammation, Macrophages, Insulin Resistance.
T
HE RECENT REPORT by Qin and colleagues (2013) on the impact of alcohol binge prior to burn trauma on localized adipose tissue inflammatory responses is of interest and potential relevance to the management of burn patients with a history of recent alcohol abuse. Alcohol intoxication is well documented to increase the prevalence of trauma. Approximately 25% of injuries treated in emergency departments are alcohol related (Cherpitel et al., 2012). However, elucidating the impact of alcohol on clinical outcomes from traumatic injury is difficult to determine because of variables such as prior health status, genetics, and severity of injury, all of which can be controlled in the laboratory setting. Although small animal (preclinical) studies have some limitations, significant advances in our knowledge can be from models controlling for these factors. In particular, the role of
From the Louisiana State University Health Science Center Department of Physiology and Alcohol and Drug Abuse Center (PEM), New Orleans, Louisiana. Received for publication August 30, 2013; accepted September 10, 2013. Reprint requests: Patricia E. Molina, MD, PhD, Louisiana State University Health Science Center Department of Physiology and Alcohol and Drug Abuse Center, 1901 Perdido St., New Orleans, LA 70112; Tel.: 504568-6187; Fax: 504-568-6158; E-mail: [email protected] Copyright © 2013 by the Research Society on Alcoholism. DOI: 10.1111/acer.12296 Alcohol Clin Exp Res, Vol 38, No 1, 2014: pp 33–35
alcohol intoxication, during the period preceding injury, on outcomes has been difficult to dissect from clinical studies. Controlled dose and timing of alcohol administration, as well as homogeneity in the severity of the insult, have provided insight into the specific aspects of the host defense mechanisms that are impaired during acute alcohol intoxication. Qin and colleagues (2013) used intraperitoneal alcohol administration to achieve blood alcohol concentrations of approximately 150 mg/dl to investigate its impact on adipose tissue inflammation following burn injury. These alcohol levels are above the legal limit and are considered to reflect levels achieved during binge drinking. Furthermore, they are well within the range of alcohol levels detected in trauma victims at the time of entry to the emergency room. The burn injury model used by these investigators provides a controlled approach to the study of an injury with significantly complex pathophysiology. Qin and colleagues’ (2013) study focused on the impact of alcohol binge prior to burn trauma on localized adipose tissue inflammatory responses. Their results provide evidence of a marked increase in adipose inflammation during the postburn period. Alcohol intoxication has detrimental effects on multiple aspects critical to the host response to injury, including expression and processing of cytokines and chemokines, expression of adhesion molecules, recruitment and accumulation of inflammatory cells, and macrophage oxidative capacity. Derangement of all of these 33
34
mechanisms is likely to significantly exacerbate morbidity and mortality in the alcohol-intoxicated trauma victim. Our preclinical studies have provided evidence that acute alcohol intoxication results in marked alteration of the immediate metabolic, hemodynamic, and proinflammatory responses to traumatic injury (Molina et al., 2013). In addition, we have observed accentuated inflammation in spleen and lung following hemorrhagic shock in alcohol-intoxicated rodents; similar to the accentuated inflammatory phenotype detected in adipose tissue in Qin and colleagues’ study (Molina et al., 2013). The integrity of the inflammatory response is critical for host defense, wound healing, and tissue repair. And its dysregulation, exaggerated in either magnitude or duration, is detrimental to the host. Exacerbated and prolonged tissue inflammation has been proposed as a central mechanism of alcohol-mediated tissue injury (McClain et al., 2004; Szabo et al., 2007). Thus, timely resolution of inflammation is considered to be necessary in restoring tissue homeostasis. While the role of inflammatory responses has been considered to be critical in host defense from secondary challenges, the potential impact of these changes on additional biomedical consequences from injury has not been previously explored. This is particularly relevant for the burn-injured host. The postburn period is characterized by hypermetabolic and catabolic responses associated with insulin resistance. Among the alterations associated with this period are elevated insulin, cortisol, and resistin levels and decreased leptin, adiponectin, and ghrelin levels. These endocrine and adipokine changes are thought to be the result of inflammatory responses (Wade et al., 2013). The observation that alcohol accentuated adipose tissue inflammation following burn has important implications for the functional integrity of this tissue. Up-regulation of inflammatory cytokines has been reported to contribute to dysregulation of adipose tissue metabolism (Hajer et al., 2008). Elevated expression of proinflammatory cytokines and adipokines has been linked to alterations in metabolism in obese individuals (Rasouli and Kern, 2008). Thus, one can predict that the alcohol-enhanced inflammatory adipose tissue phenotype reported by Qin and colleagues (2013) is likely to have lingering effects on metabolic control of glucose and lipid metabolism. Hyperglycemia and deranged metabolic control during the postinjury period has been reported to be a significant factor in patient outcomes (Jeschke et al., 2008). Failure to achieve early glycemic control in patients with burn injury is associated with an increased risk of mortality (Murphy et al., 2011). This is critical not only for the management of the immediate postinjury period, but because stress-induced insulin resistance following burn has been shown to persist for up to 3 years (Gauglitz et al., 2009). The Qin and colleagues (2013) burn study in a rodent model also showed that adiponectin expression in adipose tissue was suppressed following a single alcohol binge, but not altered following multiple binges. Adiponectin is consid-
MOLINA
ered an anti-inflammatory adipokine that suppresses proinflammatory and stimulates anti-inflammatory cytokine expression, in addition to promoting the differentiation of anti-inflammatory M2 macrophages and apoptotic cell phagocytosis. Hence, changes in its expression may have a profound impact on the inflammatory cascade (Kwon and Pessin, 2013). The adipose tissue environment following burn injury in the alcohol-intoxicated animals may therefore reflect the result of multiple inflammatory pathways, including cytokine, chemokine, and adipokine alterations. Unfortunately, no additional assays were done to reflect the status of other adipokines or of alterations in metabolic control during the postinjury period. Thus, the possibility that enhanced adipose tissue inflammation may lead to additional disruption of adipokine release or responsiveness, and subsequent metabolic dysregulation contributing to the insulin resistant state of the postburn period remains to be explored. The impact of alcohol abuse on adipose tissue mass and phenotype has not been investigated systematically. Studies have reported that chronic alcohol consumption is associated with decreased fat mass, which has been attributed to altered neuroendocrine function resulting in increased cortisol release (Leggio et al., 2009). In contrast, others have reported a high incidence of dyslipidemia and increased fat mass in alcoholics with more than 20% of patients meeting criteria for metabolic syndrome (Jarvis et al., 2007). In addition, alcohol has been shown to disrupt adipokine profiles such as that of leptin (Nicolas et al., 2001) and adiponectin (Rogers et al., 2008) and promote macrophage infiltration into adipose tissue. These alterations in adipose tissue phenotype are attributed to oxidative stress resulting from alcohol metabolism (Tang et al., 2012) and are associated with hepatic and adipose tissue insulin resistance (Kang et al., 2007). The relevance of enhanced adipose inflammatory responses during the postburn period is likely an important risk factor for the development of peripheral tissue insulin resistance. While the causal relationship between inflammation and endocrine regulation of glucose and lipid metabolism is still not completely understood, several lines of evidence support a close immune–endocrine interaction that can potentially affect regulation of metabolism. Studies have reported that leptin treatment reduces burn-induced increase in granulocyte and mononuclear cell death, suggesting a role for adipokines in modulating inflammation and, ultimately, tissue injury (Cakir et al., 2005). Leptin and adiponectin have been reported to have contrasting effects on inflammatory responses, and modulations in their expression have been linked to insulin resistance. However, an interesting finding from Qin and colleagues’ (2013) study is the identification of the formation of crown-like structures in adipose tissue obtained from alcohol-intoxicated burned animals. Crownlike structures represent an interface between dead adipocytes and tissue inflammatory cells and have been suggested to correlate not only with obesity and insulin resistance but with cardiovascular disease (West, 2009). The implications of
COMMENTARY
35
adipose tissue remodeling reflected in epididymal fat in Qin and colleagues’ study remains to be explored. Increasing evidence points to alcohol interacting with the pathophysiological responses to stressors such as traumatic injury and infection. Recognition of tissue-specific alterations that can contribute to comorbid conditions in alcohol-abusing individuals is increasing as investigators provide supporting evidence for a systemic effect of alcohol that may interfere with multiple organ systems. The results from Qin and colleagues’ (2013) study add to that body of literature by identifying a potential mechanism by which alcohol abuse and injury can synergize to promote a dysregulated environment conducive to insulin resistance, hyperglycemia, and potentially metabolic syndrome if the inflammatory changes in adipose tissue observed were to be sustained over prolonged periods. Studies are needed to elucidate the overall impact of these localized alterations to glycemic management and control during the postinjury period. The relevance of metabolic dysregulation during the period following burn injury is significant due to the complexities in the management of these patients and the difficulty in controlling glycemia and its subsequent impact on outcomes. Furthermore, it is plausible that similar disruptions in the balance between inflammatory and anti-inflammatory adipokine expression may extend to other injuries. Preclinical studies are needed to provide better understanding of the mechanisms involved in alcohol-enhanced adipose inflammation. In addition, increased awareness of the existence of an alcohol use disorder in burn or trauma victims should positively impact patient management and care during the postinjury period. ACKNOWLEDGMENTS The author is grateful for editorial support from Michael G. Levitzky, PhD and Betsy Giaimo. The author’s research is supported by NIAAA-07577, NIAAA-09803, UAA02199 5A, and AA-11290. REFERENCES Cakir B, Cevik H, Contuk G, Ercan F, Eksßioglu-Demiralp E, Yegen BC (2005) Leptin ameliorates burn-induced multiple organ damage and modulates postburn immune response in rats. Regul Pept 125:135–144. Cherpitel CJ, Ye Y, Bond J, Borges G, Chou P, Nilsen P, Ruan J, Xiang X (2012) Multi-level analysis of alcohol-related injury and drinking pattern: emergency department data from 19 countries. Addiction 107:1263–1272.
Gauglitz GG, Herndon DN, Kulp GA, Meyer WJ 3rd, Jeschke MG (2009) Abnormal insulin sensitivity persists up to three years in pediatric patients post-burn. J Clin Endocrinol Metab 94:1656–1664. Hajer GR, van Haeften TW, Visseren FL (2008) Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 29:2959–2971. Jarvis CM, Hayman LL, Braun LT, Schwertz DW, Ferrans CE, Piano MR (2007) Cardiovascular risk factors and metabolic syndrome in alcoholand nicotine-dependent men and women. J Cardiovasc Nurs 22:429–435. Jeschke MG, Chinkes DL, Finnerty CC, Kulp G, Suman OE, Norbury WB, Branski LK, Gauglitz GG, Mlcak RP, Herndon DN (2008) Pathophysiologic response to severe burn injury. Ann Surg 248:387–401. Kang L, Sebastian BM, Pritchard MT, Pratt BT, Previs SF, Nagy LE (2007) Chronic ethanol-induced insulin resistance is associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines. Alcohol Clin Exp Res 31:1581–1588. Kwon H, Pessin JE (2013) Adipokines mediate inflammation and insulin resistance. Front Endocrinol (Lausanne) 4:71. Leggio L, Malandrino N, Ferrulli A, Cardone S, Miceli A, Gasbarrini G, Capristo E, Addolorato G (2009) Is cortisol involved in the alcohol-related fat mass impairment? A longitudinal clinical study. Alcohol Alcohol 44:211–215. McClain CJ, Song Z, Barve SS, Hill DB, Deaciuc I (2004) Recent advances in alcoholic liver disease. IV. Dysregulated cytokine metabolism in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 287:G497– G502. Molina PE, Sulzer JK, Whitaker AM (2013) Alcohol abuse and the injured host: dysregulation of counterregulatory mechanisms review. Shock 39:240–249. Murphy CV, Coffey R, Cook CH, Gerlach AT, Miller SF (2011) Early glycemic control in critically ill patients with burn injury. J Burn Care Res 32:583–590. Nicolas JM, Fernandez-Sola J, Fatj o F, Casamitjana R, Bataller R, Sacanella E, Tobıas E, Badıa E, Estruch R (2001) Increased circulating leptin levels in chronic alcoholism. Alcohol Clin Exp Res 25:83–88. Qin Y, Hamilton JL, Bird MD, Chen MM, Ramirez L, Zahs A, Kovacs EJ, Makowski L (2013) Adipose inflammation and macrophage infiltration after binge ethanol and burn injury. Alcohol Clin Exp Res. doi:10.1111/ acer.12210 [Epub ahead of print]. Rasouli N, Kern PA (2008) Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 93 (11 Suppl 1):S64–S73. Rogers CQ, Ajmo JM, You M (2008) Adiponectin and alcoholic fatty liver disease. IUBMB Life 60:790–797. Szabo G, Mandrekar P, Oak S, Mayerle J (2007) Effect of ethanol on inflammatory responses. Implications for pancreatitis. Pancreatology 7:115–123. Tang H, Sebastian BM, Axhemi A, Chen X, Hillian AD, Jacobsen DW, Nagy LE (2012) Ethanol-induced oxidative stress via the CYP2E1 pathway disrupts adiponectin secretion from adipocytes. Alcohol Clin Exp Res 36:214–222. Wade CE, Mora AG, Shields BA, Pidcoke HF, Baer LA, Chung KK, Wolf SE (2013) Signals from fat after injury: plasma adipokines and ghrelin concentrations in the severely burned. Cytokine 61:78–83. West M (2009) Dead adipocytes and metabolic dysfunction: recent progress. Curr Opin Endocrinol Diabetes Obes 16:178–182.
Copyright of Alcoholism: Clinical & Experimental Research is the property of WileyBlackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Vol. 38, No. 1 January 2014
Alcohol Binging Exacerbates Adipose Tissue Inflammation Following Burn Injury Patricia E. Molina
Background: Alcohol intoxication resulting from binge-drinking episodes is a leading cause of traumatic injury. Alcohol affects systemic responses critical for restoring homeostasis during the postinjury period. The lingering consequences of alcohol intoxication at time of injury are of relevance to the management of the trauma victim. Methods: The study by Qin and colleagues (2013) used intraperitoneal alcohol administration to achieve blood alcohol concentrations of approximately 150 mg/dl to investigate its impact on adipose tissue inflammation following burn injury in a rodent model. The report and the pertinent literature were reviewed to provide perspective on the findings. Results: Their results provide evidence of a marked increase in adipose inflammation during the postburn period. These findings identify a potential mechanism by which alcohol abuse and injury can synergize to promote a dysregulated environment conducive to insulin resistance, hyperglycemia, and potentially metabolic syndrome if the inflammatory changes in adipose tissue observed were to be sustained over prolonged periods. Conclusions: Adipose tissue inflammation potentially leading to metabolic dysregulation during the period following burn injury may further add to the complexities in the management of these patients. The underlying mechanisms need further investigation. The existence of an alcohol use disorder in burn or trauma victims should lead to increased awareness of possible metabolic complications during the recovery period that could be explained by enhanced adipose tissue inflammation. Key Words: Alcohol Binge, Burn Injury, Adipose, Inflammation, Macrophages, Insulin Resistance.
T
HE RECENT REPORT by Qin and colleagues (2013) on the impact of alcohol binge prior to burn trauma on localized adipose tissue inflammatory responses is of interest and potential relevance to the management of burn patients with a history of recent alcohol abuse. Alcohol intoxication is well documented to increase the prevalence of trauma. Approximately 25% of injuries treated in emergency departments are alcohol related (Cherpitel et al., 2012). However, elucidating the impact of alcohol on clinical outcomes from traumatic injury is difficult to determine because of variables such as prior health status, genetics, and severity of injury, all of which can be controlled in the laboratory setting. Although small animal (preclinical) studies have some limitations, significant advances in our knowledge can be from models controlling for these factors. In particular, the role of
From the Louisiana State University Health Science Center Department of Physiology and Alcohol and Drug Abuse Center (PEM), New Orleans, Louisiana. Received for publication August 30, 2013; accepted September 10, 2013. Reprint requests: Patricia E. Molina, MD, PhD, Louisiana State University Health Science Center Department of Physiology and Alcohol and Drug Abuse Center, 1901 Perdido St., New Orleans, LA 70112; Tel.: 504568-6187; Fax: 504-568-6158; E-mail: [email protected] Copyright © 2013 by the Research Society on Alcoholism. DOI: 10.1111/acer.12296 Alcohol Clin Exp Res, Vol 38, No 1, 2014: pp 33–35
alcohol intoxication, during the period preceding injury, on outcomes has been difficult to dissect from clinical studies. Controlled dose and timing of alcohol administration, as well as homogeneity in the severity of the insult, have provided insight into the specific aspects of the host defense mechanisms that are impaired during acute alcohol intoxication. Qin and colleagues (2013) used intraperitoneal alcohol administration to achieve blood alcohol concentrations of approximately 150 mg/dl to investigate its impact on adipose tissue inflammation following burn injury. These alcohol levels are above the legal limit and are considered to reflect levels achieved during binge drinking. Furthermore, they are well within the range of alcohol levels detected in trauma victims at the time of entry to the emergency room. The burn injury model used by these investigators provides a controlled approach to the study of an injury with significantly complex pathophysiology. Qin and colleagues’ (2013) study focused on the impact of alcohol binge prior to burn trauma on localized adipose tissue inflammatory responses. Their results provide evidence of a marked increase in adipose inflammation during the postburn period. Alcohol intoxication has detrimental effects on multiple aspects critical to the host response to injury, including expression and processing of cytokines and chemokines, expression of adhesion molecules, recruitment and accumulation of inflammatory cells, and macrophage oxidative capacity. Derangement of all of these 33
34
mechanisms is likely to significantly exacerbate morbidity and mortality in the alcohol-intoxicated trauma victim. Our preclinical studies have provided evidence that acute alcohol intoxication results in marked alteration of the immediate metabolic, hemodynamic, and proinflammatory responses to traumatic injury (Molina et al., 2013). In addition, we have observed accentuated inflammation in spleen and lung following hemorrhagic shock in alcohol-intoxicated rodents; similar to the accentuated inflammatory phenotype detected in adipose tissue in Qin and colleagues’ study (Molina et al., 2013). The integrity of the inflammatory response is critical for host defense, wound healing, and tissue repair. And its dysregulation, exaggerated in either magnitude or duration, is detrimental to the host. Exacerbated and prolonged tissue inflammation has been proposed as a central mechanism of alcohol-mediated tissue injury (McClain et al., 2004; Szabo et al., 2007). Thus, timely resolution of inflammation is considered to be necessary in restoring tissue homeostasis. While the role of inflammatory responses has been considered to be critical in host defense from secondary challenges, the potential impact of these changes on additional biomedical consequences from injury has not been previously explored. This is particularly relevant for the burn-injured host. The postburn period is characterized by hypermetabolic and catabolic responses associated with insulin resistance. Among the alterations associated with this period are elevated insulin, cortisol, and resistin levels and decreased leptin, adiponectin, and ghrelin levels. These endocrine and adipokine changes are thought to be the result of inflammatory responses (Wade et al., 2013). The observation that alcohol accentuated adipose tissue inflammation following burn has important implications for the functional integrity of this tissue. Up-regulation of inflammatory cytokines has been reported to contribute to dysregulation of adipose tissue metabolism (Hajer et al., 2008). Elevated expression of proinflammatory cytokines and adipokines has been linked to alterations in metabolism in obese individuals (Rasouli and Kern, 2008). Thus, one can predict that the alcohol-enhanced inflammatory adipose tissue phenotype reported by Qin and colleagues (2013) is likely to have lingering effects on metabolic control of glucose and lipid metabolism. Hyperglycemia and deranged metabolic control during the postinjury period has been reported to be a significant factor in patient outcomes (Jeschke et al., 2008). Failure to achieve early glycemic control in patients with burn injury is associated with an increased risk of mortality (Murphy et al., 2011). This is critical not only for the management of the immediate postinjury period, but because stress-induced insulin resistance following burn has been shown to persist for up to 3 years (Gauglitz et al., 2009). The Qin and colleagues (2013) burn study in a rodent model also showed that adiponectin expression in adipose tissue was suppressed following a single alcohol binge, but not altered following multiple binges. Adiponectin is consid-
MOLINA
ered an anti-inflammatory adipokine that suppresses proinflammatory and stimulates anti-inflammatory cytokine expression, in addition to promoting the differentiation of anti-inflammatory M2 macrophages and apoptotic cell phagocytosis. Hence, changes in its expression may have a profound impact on the inflammatory cascade (Kwon and Pessin, 2013). The adipose tissue environment following burn injury in the alcohol-intoxicated animals may therefore reflect the result of multiple inflammatory pathways, including cytokine, chemokine, and adipokine alterations. Unfortunately, no additional assays were done to reflect the status of other adipokines or of alterations in metabolic control during the postinjury period. Thus, the possibility that enhanced adipose tissue inflammation may lead to additional disruption of adipokine release or responsiveness, and subsequent metabolic dysregulation contributing to the insulin resistant state of the postburn period remains to be explored. The impact of alcohol abuse on adipose tissue mass and phenotype has not been investigated systematically. Studies have reported that chronic alcohol consumption is associated with decreased fat mass, which has been attributed to altered neuroendocrine function resulting in increased cortisol release (Leggio et al., 2009). In contrast, others have reported a high incidence of dyslipidemia and increased fat mass in alcoholics with more than 20% of patients meeting criteria for metabolic syndrome (Jarvis et al., 2007). In addition, alcohol has been shown to disrupt adipokine profiles such as that of leptin (Nicolas et al., 2001) and adiponectin (Rogers et al., 2008) and promote macrophage infiltration into adipose tissue. These alterations in adipose tissue phenotype are attributed to oxidative stress resulting from alcohol metabolism (Tang et al., 2012) and are associated with hepatic and adipose tissue insulin resistance (Kang et al., 2007). The relevance of enhanced adipose inflammatory responses during the postburn period is likely an important risk factor for the development of peripheral tissue insulin resistance. While the causal relationship between inflammation and endocrine regulation of glucose and lipid metabolism is still not completely understood, several lines of evidence support a close immune–endocrine interaction that can potentially affect regulation of metabolism. Studies have reported that leptin treatment reduces burn-induced increase in granulocyte and mononuclear cell death, suggesting a role for adipokines in modulating inflammation and, ultimately, tissue injury (Cakir et al., 2005). Leptin and adiponectin have been reported to have contrasting effects on inflammatory responses, and modulations in their expression have been linked to insulin resistance. However, an interesting finding from Qin and colleagues’ (2013) study is the identification of the formation of crown-like structures in adipose tissue obtained from alcohol-intoxicated burned animals. Crownlike structures represent an interface between dead adipocytes and tissue inflammatory cells and have been suggested to correlate not only with obesity and insulin resistance but with cardiovascular disease (West, 2009). The implications of
COMMENTARY
35
adipose tissue remodeling reflected in epididymal fat in Qin and colleagues’ study remains to be explored. Increasing evidence points to alcohol interacting with the pathophysiological responses to stressors such as traumatic injury and infection. Recognition of tissue-specific alterations that can contribute to comorbid conditions in alcohol-abusing individuals is increasing as investigators provide supporting evidence for a systemic effect of alcohol that may interfere with multiple organ systems. The results from Qin and colleagues’ (2013) study add to that body of literature by identifying a potential mechanism by which alcohol abuse and injury can synergize to promote a dysregulated environment conducive to insulin resistance, hyperglycemia, and potentially metabolic syndrome if the inflammatory changes in adipose tissue observed were to be sustained over prolonged periods. Studies are needed to elucidate the overall impact of these localized alterations to glycemic management and control during the postinjury period. The relevance of metabolic dysregulation during the period following burn injury is significant due to the complexities in the management of these patients and the difficulty in controlling glycemia and its subsequent impact on outcomes. Furthermore, it is plausible that similar disruptions in the balance between inflammatory and anti-inflammatory adipokine expression may extend to other injuries. Preclinical studies are needed to provide better understanding of the mechanisms involved in alcohol-enhanced adipose inflammation. In addition, increased awareness of the existence of an alcohol use disorder in burn or trauma victims should positively impact patient management and care during the postinjury period. ACKNOWLEDGMENTS The author is grateful for editorial support from Michael G. Levitzky, PhD and Betsy Giaimo. The author’s research is supported by NIAAA-07577, NIAAA-09803, UAA02199 5A, and AA-11290. REFERENCES Cakir B, Cevik H, Contuk G, Ercan F, Eksßioglu-Demiralp E, Yegen BC (2005) Leptin ameliorates burn-induced multiple organ damage and modulates postburn immune response in rats. Regul Pept 125:135–144. Cherpitel CJ, Ye Y, Bond J, Borges G, Chou P, Nilsen P, Ruan J, Xiang X (2012) Multi-level analysis of alcohol-related injury and drinking pattern: emergency department data from 19 countries. Addiction 107:1263–1272.
Gauglitz GG, Herndon DN, Kulp GA, Meyer WJ 3rd, Jeschke MG (2009) Abnormal insulin sensitivity persists up to three years in pediatric patients post-burn. J Clin Endocrinol Metab 94:1656–1664. Hajer GR, van Haeften TW, Visseren FL (2008) Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 29:2959–2971. Jarvis CM, Hayman LL, Braun LT, Schwertz DW, Ferrans CE, Piano MR (2007) Cardiovascular risk factors and metabolic syndrome in alcoholand nicotine-dependent men and women. J Cardiovasc Nurs 22:429–435. Jeschke MG, Chinkes DL, Finnerty CC, Kulp G, Suman OE, Norbury WB, Branski LK, Gauglitz GG, Mlcak RP, Herndon DN (2008) Pathophysiologic response to severe burn injury. Ann Surg 248:387–401. Kang L, Sebastian BM, Pritchard MT, Pratt BT, Previs SF, Nagy LE (2007) Chronic ethanol-induced insulin resistance is associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines. Alcohol Clin Exp Res 31:1581–1588. Kwon H, Pessin JE (2013) Adipokines mediate inflammation and insulin resistance. Front Endocrinol (Lausanne) 4:71. Leggio L, Malandrino N, Ferrulli A, Cardone S, Miceli A, Gasbarrini G, Capristo E, Addolorato G (2009) Is cortisol involved in the alcohol-related fat mass impairment? A longitudinal clinical study. Alcohol Alcohol 44:211–215. McClain CJ, Song Z, Barve SS, Hill DB, Deaciuc I (2004) Recent advances in alcoholic liver disease. IV. Dysregulated cytokine metabolism in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 287:G497– G502. Molina PE, Sulzer JK, Whitaker AM (2013) Alcohol abuse and the injured host: dysregulation of counterregulatory mechanisms review. Shock 39:240–249. Murphy CV, Coffey R, Cook CH, Gerlach AT, Miller SF (2011) Early glycemic control in critically ill patients with burn injury. J Burn Care Res 32:583–590. Nicolas JM, Fernandez-Sola J, Fatj o F, Casamitjana R, Bataller R, Sacanella E, Tobıas E, Badıa E, Estruch R (2001) Increased circulating leptin levels in chronic alcoholism. Alcohol Clin Exp Res 25:83–88. Qin Y, Hamilton JL, Bird MD, Chen MM, Ramirez L, Zahs A, Kovacs EJ, Makowski L (2013) Adipose inflammation and macrophage infiltration after binge ethanol and burn injury. Alcohol Clin Exp Res. doi:10.1111/ acer.12210 [Epub ahead of print]. Rasouli N, Kern PA (2008) Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 93 (11 Suppl 1):S64–S73. Rogers CQ, Ajmo JM, You M (2008) Adiponectin and alcoholic fatty liver disease. IUBMB Life 60:790–797. Szabo G, Mandrekar P, Oak S, Mayerle J (2007) Effect of ethanol on inflammatory responses. Implications for pancreatitis. Pancreatology 7:115–123. Tang H, Sebastian BM, Axhemi A, Chen X, Hillian AD, Jacobsen DW, Nagy LE (2012) Ethanol-induced oxidative stress via the CYP2E1 pathway disrupts adiponectin secretion from adipocytes. Alcohol Clin Exp Res 36:214–222. Wade CE, Mora AG, Shields BA, Pidcoke HF, Baer LA, Chung KK, Wolf SE (2013) Signals from fat after injury: plasma adipokines and ghrelin concentrations in the severely burned. Cytokine 61:78–83. West M (2009) Dead adipocytes and metabolic dysfunction: recent progress. Curr Opin Endocrinol Diabetes Obes 16:178–182.
Copyright of Alcoholism: Clinical & Experimental Research is the property of WileyBlackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
