- Email: [email protected]
Leptin: Is it a possible specific liver drug for non-alcoholic fatty liver disease (NAFLD)?
462
Correspondence
Figure 2 Diagrammatic representation of the hypothesis of altered cerebrospinal fluid dynamics in pathogenesis of multilevel myelopathy with single spinal stenosis. (A) CSF flow dynamics in a segmental myelopathic patient with single spinal stenosis. CSF flow is normal. CSF flows from the subarachnoid space (SAS) between the arachnoid (A) and pia (P) to the subpial space, and then enters the perivascular space (PVS). CSF circulates through the cord parenchyma toward the central canal (CC), but also flows in reverse, as these forces are relatively balanced. (B) Altered CSF flow dynamics in a multilevel myelopathic patient undergoing single spinal stenosis. Net CSF flow enters into the spinal cord parenchyma; however, because of abnormal CSF flow, fluid can accumulate within subtotal spinal cord, resulting in interstitial edema within the spinal cord.
References [1] Fehlings MG, Skaf G. A review of the pathophysiology of cervical spondylotic myelopathy with insights for potential novel mechanisms drawn from traumatic spinal cord injury. Spine 1998;23:2730–7. [2] Batzdorf U, Flannigan BD. Surgical decompressive procedures for cervical spondylotic myelopathy. A study using magnetic resonance imaging. Spine 1991;16:123–7. [3] Gooding MR, Wilson CB, Hoff JT. Experimental cervical myelopathy: effects of ischemia and compression of the canine cervical spinal cord. J Neurosurg 1975;43: 9–17. [4] Pathak M, Kim RC, Pribram H. Spinal cord infarction following vertebral angiography: clinical and pathological findings. J Spinal Cord Med 2000;23:92–5. [5] George B, Gauthier N, Lot G. Multisegmental cervical spondylotic myelopathy and radiculopathy treated by multilevel oblique corpectomies without fusion. Neurosurgery 1999;44:81–90. [6] Punjaisee S. Laminectomy and postero-lateral mass plating for multilevel cervical spondylotic myelopathy. J Med Assoc Thai 2004;87:768–73. [7] Rusbridge C, Greitz D, Iskandar BJ. Syringomyelia: current concepts in pathogenesis, diagnosis, and treatment. J Vet Intern Med 2006;20:469–79.
[8] Koyanagi I, Iwasaki Y, Hida K, Houkin K. Clinical features and pathomechanisms of syringomyelia associated with spinal arachnoiditis. Surg Neurol 2005;63:350–5. (discussion 355-6).
Hua Han Ya-Yi Xia Bing-Ren Gao * Institute of Orthopaedics, The Second Affiliated Hospital, Lanzhou University, Lanzhou 730030, PR China * Tel.: +86 0931 8942580; fax: +86 0931 8942579 E-mail address: [email protected] (B.-R. Gao) Shuan-Ke Wang Bin Zhao Department of Orthopaedics, The Second Affiliated Hospital, Lanzhou University, Lanzhou 730030, PR China
doi:10.1016/j.mehy.2008.04.010
Leptin: Is it a possible specific liver drug for non-alcoholic fatty liver disease (NAFLD)? Non-alcoholic fatty liver disease (NAFLD) is a condition of emerging relevance that includes different forms of chronic liver damage, from a simple fatty
infiltration (steatosis) of hepatocytes to steatohepatitis (NASH) with fibrosis. This last form may evolve to cirrhosis and hepatocellular carcinoma [1].
Correspondence Theoretically, only patients with non-alcoholic steatohepatitis (NASH) need to be treated, as only NASH may evolve to cirrhosis. In our opinion, liver steatosis is present in young patients, it could be a predictive factor of death from cardio-vascular diseases other than hepatocellular carcinoma, as well as of the onset of type 2 diabetes. These considerations strongly indicate the necessity to treat each stage of NAFLD. Currently, there are no effective drugs for NASH, as NASH’s natural history and prognosis are not well understood. Consequently, therapy of patients with non-alcoholic fatty liver has typically been focused on the management of associated conditions such as obesity, diabetes mellitus, and hyperlipidemia. No specific drug is actually present to treat liver steatosis or NASH. The treatment of NAFLD depends on the individual characteristics of each patient. Diet and physical exercise may be considered a basal universal approach. Specific liver drugs for NAFLD are needed in the future research [2]. Leptin, the ob gene product [3] secreted by adipocytes, is a 167-aa protein and is important in the regulation of energy balance. Leptin reduced food intake and body weight intracerebrally [4]. In essence, leptin system should not only be as a target for anti-obesity therapy. Recent data has explored the effect of leptin infusion on the pathogenesis of diet-induced lipodystrophy in mice. The results indicate that leptin infusion can attenuate hepatic steatosis and hyperinsulinemia through the reduction of hepatic triglyceride synthesis and the improvement of insulin sensitivity in diet-induced lipodystrophy model mice [5]. NAFLD is frequently associated with overweight or obesity. Overweight and obesity lead to the occurrence of other metabolic disorders, which were predictive factors of NAFLD [6,7] such as diabetes and dyslipidaemia. In the pathophysiology of NAFLD, greater importance is attached to obesity, weight loss is usually recommended as first-line management for these patients [8], while weight loss could be achieved by diet restriction, physical exercise and anti-obesity drugs such as leptin infusion. With the mechanisms including anti-obesity, attenuating hepatic steatosis and hyperinsulinemia through the reduction of hepatic triglyceride synthesis and the improvement of insulin sensitivity, we propose that leptin is a possible specific liver drug for NAFLD in the future.
doi:10.1016/j.mehy.2008.04.008
463
References [1] Evert M, Dombrowski F. Hepatocellular carcinoma in the non-cirrhotic liver. Pathologe 2008;29(1):47–52. [2] Federico A, Niosi M, Vecchio Blanco CD, Loguercio C. Emerging drugs for non-alcoholic fatty liver disease. Expert Opin Emerg Drugs 2008;13(1):145–58. [3] Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372(6505): 425–32. [4] Mistry AM, Swick AG, Romsos DR. Leptin rapidly lowers food intake and elevates metabolic rates in lean and ob/ob mice. J Nutr 1997;127:2065–72. [5] Nagao Koji, Inoue Nao, Ujino Yoko, Higa Kouki, Shirouchi Yu-Ming, Wang Yu-Ming, et al. Effect of leptin infusion on insulin sensitivity and lipid metabolism in dietinduced lipodystrophy model mice. Lipids Health Dis 2008;7:8. [6] Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007;30(5): 1212–8. [7] Solga SF, Clark JM, Alkhuraishi AR, Torbenson M, Tabesh A, Schweitzer M, et al. Race and comorbid factors predict nonalcoholic fatty liver disease histopathology in severely obese patients. Surg Obes Relat Dis 2005;1(1):6–11. [8] American Gastroenterological Association Medical Position Statement. Nonalcoholic fatty liver disease. Gastroenterology 2002;123:1702–4.
Yong-Ning Xin Qingdao Municipal Hospital, Qingdao 266021, Shandong Province, China Shi-Ying Xuan Qingdao Municipal Hospital, Qingdao 266021, Shandong Province, China College of Medicine and Pharmaceutics, Ocean University of China, 5 Yushan Road, Qingdao 266003, China Tel.: +86 532 88905508; fax: +86 532 82031522 E-mail address: [email protected] Hua-Shi Guan College of Medicine and Pharmaceutics, Ocean University of China, 5 Yushan Road, Qingdao 266003, China
Correspondence
Figure 2 Diagrammatic representation of the hypothesis of altered cerebrospinal fluid dynamics in pathogenesis of multilevel myelopathy with single spinal stenosis. (A) CSF flow dynamics in a segmental myelopathic patient with single spinal stenosis. CSF flow is normal. CSF flows from the subarachnoid space (SAS) between the arachnoid (A) and pia (P) to the subpial space, and then enters the perivascular space (PVS). CSF circulates through the cord parenchyma toward the central canal (CC), but also flows in reverse, as these forces are relatively balanced. (B) Altered CSF flow dynamics in a multilevel myelopathic patient undergoing single spinal stenosis. Net CSF flow enters into the spinal cord parenchyma; however, because of abnormal CSF flow, fluid can accumulate within subtotal spinal cord, resulting in interstitial edema within the spinal cord.
References [1] Fehlings MG, Skaf G. A review of the pathophysiology of cervical spondylotic myelopathy with insights for potential novel mechanisms drawn from traumatic spinal cord injury. Spine 1998;23:2730–7. [2] Batzdorf U, Flannigan BD. Surgical decompressive procedures for cervical spondylotic myelopathy. A study using magnetic resonance imaging. Spine 1991;16:123–7. [3] Gooding MR, Wilson CB, Hoff JT. Experimental cervical myelopathy: effects of ischemia and compression of the canine cervical spinal cord. J Neurosurg 1975;43: 9–17. [4] Pathak M, Kim RC, Pribram H. Spinal cord infarction following vertebral angiography: clinical and pathological findings. J Spinal Cord Med 2000;23:92–5. [5] George B, Gauthier N, Lot G. Multisegmental cervical spondylotic myelopathy and radiculopathy treated by multilevel oblique corpectomies without fusion. Neurosurgery 1999;44:81–90. [6] Punjaisee S. Laminectomy and postero-lateral mass plating for multilevel cervical spondylotic myelopathy. J Med Assoc Thai 2004;87:768–73. [7] Rusbridge C, Greitz D, Iskandar BJ. Syringomyelia: current concepts in pathogenesis, diagnosis, and treatment. J Vet Intern Med 2006;20:469–79.
[8] Koyanagi I, Iwasaki Y, Hida K, Houkin K. Clinical features and pathomechanisms of syringomyelia associated with spinal arachnoiditis. Surg Neurol 2005;63:350–5. (discussion 355-6).
Hua Han Ya-Yi Xia Bing-Ren Gao * Institute of Orthopaedics, The Second Affiliated Hospital, Lanzhou University, Lanzhou 730030, PR China * Tel.: +86 0931 8942580; fax: +86 0931 8942579 E-mail address: [email protected] (B.-R. Gao) Shuan-Ke Wang Bin Zhao Department of Orthopaedics, The Second Affiliated Hospital, Lanzhou University, Lanzhou 730030, PR China
doi:10.1016/j.mehy.2008.04.010
Leptin: Is it a possible specific liver drug for non-alcoholic fatty liver disease (NAFLD)? Non-alcoholic fatty liver disease (NAFLD) is a condition of emerging relevance that includes different forms of chronic liver damage, from a simple fatty
infiltration (steatosis) of hepatocytes to steatohepatitis (NASH) with fibrosis. This last form may evolve to cirrhosis and hepatocellular carcinoma [1].
Correspondence Theoretically, only patients with non-alcoholic steatohepatitis (NASH) need to be treated, as only NASH may evolve to cirrhosis. In our opinion, liver steatosis is present in young patients, it could be a predictive factor of death from cardio-vascular diseases other than hepatocellular carcinoma, as well as of the onset of type 2 diabetes. These considerations strongly indicate the necessity to treat each stage of NAFLD. Currently, there are no effective drugs for NASH, as NASH’s natural history and prognosis are not well understood. Consequently, therapy of patients with non-alcoholic fatty liver has typically been focused on the management of associated conditions such as obesity, diabetes mellitus, and hyperlipidemia. No specific drug is actually present to treat liver steatosis or NASH. The treatment of NAFLD depends on the individual characteristics of each patient. Diet and physical exercise may be considered a basal universal approach. Specific liver drugs for NAFLD are needed in the future research [2]. Leptin, the ob gene product [3] secreted by adipocytes, is a 167-aa protein and is important in the regulation of energy balance. Leptin reduced food intake and body weight intracerebrally [4]. In essence, leptin system should not only be as a target for anti-obesity therapy. Recent data has explored the effect of leptin infusion on the pathogenesis of diet-induced lipodystrophy in mice. The results indicate that leptin infusion can attenuate hepatic steatosis and hyperinsulinemia through the reduction of hepatic triglyceride synthesis and the improvement of insulin sensitivity in diet-induced lipodystrophy model mice [5]. NAFLD is frequently associated with overweight or obesity. Overweight and obesity lead to the occurrence of other metabolic disorders, which were predictive factors of NAFLD [6,7] such as diabetes and dyslipidaemia. In the pathophysiology of NAFLD, greater importance is attached to obesity, weight loss is usually recommended as first-line management for these patients [8], while weight loss could be achieved by diet restriction, physical exercise and anti-obesity drugs such as leptin infusion. With the mechanisms including anti-obesity, attenuating hepatic steatosis and hyperinsulinemia through the reduction of hepatic triglyceride synthesis and the improvement of insulin sensitivity, we propose that leptin is a possible specific liver drug for NAFLD in the future.
doi:10.1016/j.mehy.2008.04.008
463
References [1] Evert M, Dombrowski F. Hepatocellular carcinoma in the non-cirrhotic liver. Pathologe 2008;29(1):47–52. [2] Federico A, Niosi M, Vecchio Blanco CD, Loguercio C. Emerging drugs for non-alcoholic fatty liver disease. Expert Opin Emerg Drugs 2008;13(1):145–58. [3] Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372(6505): 425–32. [4] Mistry AM, Swick AG, Romsos DR. Leptin rapidly lowers food intake and elevates metabolic rates in lean and ob/ob mice. J Nutr 1997;127:2065–72. [5] Nagao Koji, Inoue Nao, Ujino Yoko, Higa Kouki, Shirouchi Yu-Ming, Wang Yu-Ming, et al. Effect of leptin infusion on insulin sensitivity and lipid metabolism in dietinduced lipodystrophy model mice. Lipids Health Dis 2008;7:8. [6] Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007;30(5): 1212–8. [7] Solga SF, Clark JM, Alkhuraishi AR, Torbenson M, Tabesh A, Schweitzer M, et al. Race and comorbid factors predict nonalcoholic fatty liver disease histopathology in severely obese patients. Surg Obes Relat Dis 2005;1(1):6–11. [8] American Gastroenterological Association Medical Position Statement. Nonalcoholic fatty liver disease. Gastroenterology 2002;123:1702–4.
Yong-Ning Xin Qingdao Municipal Hospital, Qingdao 266021, Shandong Province, China Shi-Ying Xuan Qingdao Municipal Hospital, Qingdao 266021, Shandong Province, China College of Medicine and Pharmaceutics, Ocean University of China, 5 Yushan Road, Qingdao 266003, China Tel.: +86 532 88905508; fax: +86 532 82031522 E-mail address: [email protected] Hua-Shi Guan College of Medicine and Pharmaceutics, Ocean University of China, 5 Yushan Road, Qingdao 266003, China