Inishes both basal and isoproterenol-stimulated lipolysis. Because of abundant caveats concerning 3T3L-1 cells as a model of true adipocytes for a variety of its functions, the relevance of this mechanism of lipolysis in vivo for normal physiology is unclear although the data discussed above strongly infer its potential involvement in the increases in circulating FFA in the pathophysiology accompanying insulin insufficiency/resistance via direct stimulation of ATGL activity and independently of SNS/NE and -AR activation. 9.4 Epinephrine as Initiator of Lipolysis with Exercise in Humans Despite the dominant role of the activation of WAT SNS innervation as the 487-52-5 site principal initiator of lipolysis, rather than adrenal medullary EPI as noted above, it is possible that adrenal medullary EPI, not NE, triggers lipolysis during exercise in humans. The vast majority of the data across species and treatments, however, shows that activation of the SNS innervation of WAT is the principal initiator of lipolysis in mammals. 9.5 Other Factors Affecting SNS/NE-Induced Lipolysis Recently, short chain FAs and ketone bodies have been shown to either stimulate or inhibit activation of postganglionic sympathetic neurons, respectively, via GPR41 receptors found in abundance in these cells. Stimulation of GPR41 receptors is mediated via G complex and mitogen-activated protein kinase, triggered by short chain fatty acids and opposed by the ketone -hydroxybutyrate. These data, however, are based on cardiacrelated indirect measures of SNS activity and therefore remain to be tested in SNS/NE-induced lipolysis preferably in adipose tissues. NIH-PA HC-067047 cost Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Front Neuroendocrinol. Author manuscript; available in PMC 2015 October 01. Bartness et al. Page 18 10. Sympathetic Drive to White Adipose Tissue is Not Uniform As noted above, it is critical to realize that the SNS drive to peripheral tissues is not uniform. Moreover, across WAT depots we find that the pattern of SNS drive, as measured by NETO, is seemingly unique for each lipolytic stimulus tested to date prompting us to term this a `neurochemical fingerprint’ due to this individuality and the neurochemical nature of this measure of SNS drive. As examples, cold exposure increases NETO to IWAT, EWAT, RWAT and especially IBAT, but not DWAT, whereas food deprivation increases NETO to IWAT and EWAT, but not RWAT, DWAT or IBAT. Glucoprivation, by contrast, produced by systemic injection of the non-metabolizable glucose analog, 2-deoxyglucose, increases NETO to IWAT, RWAT and DWAT, but not to EWAT or IBAT. Broad stimulation of central MC4-Rs resulting from 3V injection of MTII increases NETO only to the subcutaneous WAT pads, but not the intraabdominal WAT pads. By contrast, the longer term increase in SNS outflow produced by SD exposure of Siberian hamsters has the opposite effect, increasing NETO to the intraabdominal WAT pads, but much less so to the subcutaneous WAT. Others using laboratory rats find fat padspecific sympathetic drives to WAT depots as well. For example, with prolonged food deprivation RWAT and EWAT NETO increases, but not IBAT, whereas with acute cold exposure RWAT, EWAT and IBAT NETO increases. Clearly, these data exemplify the differential nature PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19846797 of SNS drive to WAT and BAT and emphasize the danger in generalizing the degree of SNS drive from one fat pad to another fat pad. The underlying mechanisms responsible for SNS trafficking with the.Inishes both basal and isoproterenol-stimulated lipolysis. Because of abundant caveats concerning 3T3L-1 cells as a model of true adipocytes for a variety of its functions, the relevance of this mechanism of lipolysis in vivo for normal physiology is unclear although the data discussed above strongly infer its potential involvement in the increases in circulating FFA in the pathophysiology accompanying insulin insufficiency/resistance via direct stimulation of ATGL activity and independently of SNS/NE and -AR activation. 9.4 Epinephrine as Initiator of Lipolysis with Exercise in Humans Despite the dominant role of the activation of WAT SNS innervation as the principal initiator of lipolysis, rather than adrenal medullary EPI as noted above, it is possible that adrenal medullary EPI, not NE, triggers lipolysis during exercise in humans. The vast majority of the data across species and treatments, however, shows that activation of the SNS innervation of WAT is the principal initiator of lipolysis in mammals. 9.5 Other Factors Affecting SNS/NE-Induced Lipolysis Recently, short chain FAs and ketone bodies have been shown to either stimulate or inhibit activation of postganglionic sympathetic neurons, respectively, via GPR41 receptors found in abundance in these cells. Stimulation of GPR41 receptors is mediated via G complex and mitogen-activated protein kinase, triggered by short chain fatty acids and opposed by the ketone -hydroxybutyrate. These data, however, are based on cardiacrelated indirect measures of SNS activity and therefore remain to be tested in SNS/NE-induced lipolysis preferably in adipose tissues. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Front Neuroendocrinol. Author manuscript; available in PMC 2015 October 01. Bartness et al. Page 18 10. Sympathetic Drive to White Adipose Tissue is Not Uniform As noted above, it is critical to realize that the SNS drive to peripheral tissues is not uniform. Moreover, across WAT depots we find that the pattern of SNS drive, as measured by NETO, is seemingly unique for each lipolytic stimulus tested to date prompting us to term this a `neurochemical fingerprint’ due to this individuality and the neurochemical nature of this measure of SNS drive. As examples, cold exposure increases NETO to IWAT, EWAT, RWAT and especially IBAT, but not DWAT, whereas food deprivation increases NETO to IWAT and EWAT, but not RWAT, DWAT or IBAT. Glucoprivation, by contrast, produced by systemic injection of the non-metabolizable glucose analog, 2-deoxyglucose, increases NETO to IWAT, RWAT and DWAT, but not to EWAT or IBAT. Broad stimulation of central MC4-Rs resulting from 3V injection of MTII increases NETO only to the subcutaneous WAT pads, but not the intraabdominal WAT pads. By contrast, the longer term increase in SNS outflow produced by SD exposure of Siberian hamsters has the opposite effect, increasing NETO to the intraabdominal WAT pads, but much less so to the subcutaneous WAT. Others using laboratory rats find fat padspecific sympathetic drives to WAT depots as well. For example, with prolonged food deprivation RWAT and EWAT NETO increases, but not IBAT, whereas with acute cold exposure RWAT, EWAT and IBAT NETO increases. Clearly, these data exemplify the differential nature PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19846797 of SNS drive to WAT and BAT and emphasize the danger in generalizing the degree of SNS drive from one fat pad to another fat pad. The underlying mechanisms responsible for SNS trafficking with the.
Manuscript Front Neuroendocrinol. Author manuscript; available in PMC 2015 October 01. Bartness et al. Page 18 10. Sympathetic Drive to White Adipose Tissue is Not Uniform As noted above, it is critical to realize that the SNS drive to peripheral tissues is not uniform. Moreover, across WAT depots we find that the pattern of SNS drive, as measured by NETO, is seemingly unique for each lipolytic stimulus tested to date prompting us to term this a `neurochemical fingerprint’ due to this individuality and the neurochemical nature of this measure of SNS drive. As examples, cold exposure increases NETO to IWAT, EWAT, RWAT and especially IBAT, but not DWAT, whereas food deprivation increases NETO to IWAT and EWAT, but not RWAT, DWAT or IBAT. Glucoprivation, by contrast, produced by systemic injection of the non-metabolizable glucose analog, 2-deoxyglucose, increases NETO to IWAT, RWAT and DWAT, but not to EWAT or IBAT. Broad stimulation of central MC4-Rs resulting from 3V injection of MTII increases NETO only to the subcutaneous WAT pads, but not the intraabdominal WAT pads. By contrast, the longer term increase in SNS outflow produced by SD exposure of Siberian hamsters has the opposite effect, increasing NETO to the intraabdominal WAT pads, but much less so to the subcutaneous WAT. Others using laboratory rats find fat padspecific sympathetic drives to WAT depots as well. For example, with prolonged food deprivation RWAT and EWAT NETO increases, but not IBAT, whereas with