The Experts below are selected from a list of 3513 Experts worldwide ranked by ideXlab platform
Jorgen F P Wojtaszewski - One of the best experts on this subject based on the ideXlab platform.
-
exercise alleviates lipid induced insulin resistance in human skeletal muscle signaling interaction at the level of tbc1 domain family member 4
Diabetes, 2012Co-Authors: Christian Pehmoller, Louise D Hoeg, Kim A Sjoberg, Jesper B Birk, Nina Brandt, Laurie J Goodyear, Bente Kiens, Erik A Richter, Jorgen F P WojtaszewskiAbstract:Excess lipid availability causes insulin resistance. We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle. In eight healthy young male subjects, 1 h of one-legged knee-extensor exercise was followed by 7 h of saline or Intralipid infusion. During the last 2 h, a hyperinsulinemic-euglycemic clamp was performed. Femoral catheterization and analysis of biopsy specimens enabled measurements of leg substrate balance and muscle signaling. Each subject underwent two experimental trials, differing only by saline or Intralipid infusion. Glucose infusion rate and leg glucose uptake was decreased by Intralipid. Insulin-stimulated glucose uptake was higher in the prior exercised leg in the saline and the lipid trials. In the lipid trial, prior exercise normalized insulin-stimulated glucose uptake to the level observed in the resting control leg in the saline trial. Insulin increased phosphorylation of TBC1D1/4. Whereas prior exercise enhanced TBC1D4 phosphorylation on all investigated sites compared with the rested leg, Intralipid impaired TBC1D4 S341 phosphorylation compared with the control trial. Intralipid enhanced pyruvate dehydrogenase (PDH) phosphorylation and lactate release. Prior exercise led to higher PDH phosphorylation and activation of glycogen synthase compared with resting control. In conclusion, lipid-induced insulin resistance in skeletal muscle was associated with impaired TBC1D4 S341 and elevated PDH phosphorylation. The prophylactic effect of exercise on lipid-induced insulin resistance may involve augmented TBC1D4 signaling and glycogen synthase activation.
-
lipid induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling
Diabetes, 2011Co-Authors: Louise D Hoeg, Kim A Sjoberg, Jacob Jeppesen, Thomas E Jensen, Christian Frosig, Jesper B Birk, Bruno Bisiani, Natalie Hiscock, Henriette Pilegaard, Jorgen F P WojtaszewskiAbstract:OBJECTIVE We have previously shown that overnight fasted women have higher insulin-stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism than men. We therefore hypothesized that women would be less prone to lipid-induced insulin resistance. RESEARCH DESIGN AND METHODS Insulin sensitivity of whole-body and leg glucose disposal was studied in 16 young well-matched healthy men and women infused with Intralipid or saline for 7 h. Muscle biopsies were obtained before and during a euglycemic-hyperinsulinemic clamp (1.42 mU · kg−1 · min−1). RESULTS Intralipid infusion reduced whole-body glucose infusion rate by 26% in women and 38% in men ( P < 0.05), and insulin-stimulated leg glucose uptake was reduced significantly less in women (45%) than men (60%) after Intralipid infusion. Hepatic glucose production was decreased during the clamp similarly in women and men irrespective of Intralipid infusion. Intralipid did not impair insulin or AMPK signaling in muscle and subcutaneous fat, did not cause accumulation of muscle lipid intermediates, and did not impair insulin-stimulated glycogen synthase activity in muscle or increase plasma concentrations of inflammatory cytokines. In vitro glucose transport in giant sarcolemmal vesicles was not decreased by acute exposure to fatty acids. Leg lactate release was increased and respiratory exchange ratio was decreased by Intralipid. CONCLUSIONS Intralipid infusion causes less insulin resistance of muscle glucose uptake in women than in men. This insulin resistance is not due to decreased canonical insulin signaling, accumulation of lipid intermediates, inflammation, or direct inhibition of GLUT activity. Rather, a higher leg lactate release and lower glucose oxidation with Intralipid infusion may suggest a metabolic feedback regulation of glucose metabolism.
-
pdh e1α dephosphorylation and activation in human skeletal muscle during exercise effect of Intralipid infusion
Diabetes, 2006Co-Authors: Henriette Pilegaard, Jesper B Birk, Massimo Sacchetti, Marina Mourtzakis, Graham D Hardie, Greg Stewart, Darrell P Neufer, Bengt Saltin, Gerrit Van Hall, Jorgen F P WojtaszewskiAbstract:To investigate pyruvate dehydrogenase (PDH)-E1α subunit phosphorylation and whether free fatty acids (FFAs) regulate PDH activity, seven subjects completed two trials: saline (control) and Intralipid/heparin (Intralipid). Each infusion trial consisted of a 4-h rest followed by a 3-h two-legged knee extensor exercise at moderate intensity. During the 4-h resting period, activity of PDH in the active form (PDHa) did not change in either trial, yet phosphorylation of PDH-E1α site 1 (PDH-P1) and site 2 (PDH-P2) was elevated in the Intralipid compared with the control trial. PDHa activity increased during exercise similarly in the two trials. After 3 h of exercise, PDHa activity remained elevated in the Intralipid trial but returned to resting levels in the control trial. Accordingly, in both trials PDH-P1 and PDH-P2 decreased during exercise, and the decrease was more marked during Intralipid infusion. Phosphorylation had returned to resting levels at 3 h of exercise only in the control trial. Thus, an inverse association between PDH-E1α phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1α phosphorylation, but exercise overrules this effect of FFA on PDH-E1α phosphorylation leading to even greater dephosphorylation during exercise with Intralipid infusion than with saline.
Mansoureh Eghbali - One of the best experts on this subject based on the ideXlab platform.
-
abstract 222 Intralipid induced cardioprotection in late pregnancy is fully abolished by inhibition of stat3 but not pi3k signaling pathway
Circulation Research, 2014Co-Authors: Mansoureh EghbaliAbstract:We have recently shown that the heart of late pregnant (LP) rodent is more prone to ischemia/reperfusion (I/R) injury compared to non-pregnant. Here we explored the therapeutic potential of Intralipid (ITLD) in the protection of LP hearts against I/R injury, and investigate the involvement of the signal transducer and activator of transcription-3 (STAT3) and phosphoinositide 3-kinase (PI3K) signaling pathways in ITLD-induced cardioprotetion. Isolated LP mouse hearts were subjected to 20 min ischemia followed by 40 min reperfusion with 1) Krebs Henseleit buffer (CTRL group), 2) 1% Intralipid (ITLD group) or 3) ITLD+STAT3 inhibitor Stattic (20 μM, Stattic group), and 4) ITLD+PI3K inhibitor LY294002 (45 μM). The heart function and the infarct size were measured. The Intralipid-induced cardioprotection was fully abolished by Stattic, as RPP was significantly lower in the presence of Stattic (RPP=8881±1331 mmHg*beats/min vs. 1186±563 mmHg*beats/min in ITLD+Stattic, p<0.01) at the end of reperfusion. In fact, all of the hemodynamic indexes in ITLD+Stattic were not significantly different from CTRL. The infarct size was also significantly larger in ITLD+Stattic group when compared to Intralipid alone (47.9±2.5% in ITLD+Stattic vs. 21.7±2.6 % in ITLD, p<0.01). The Intralipid-induced cardioprotection was only partially abolished by LY294002, as at the end of 40 min reperfusion the RPP was significantly lower compared to the group treated with Intralipid alone, but still significantly higher than ITLD+Stattic ((RPP=8881±1331 mmHg*beats/min in ITLD vs. 5212±1955 mmHg*beats/min in ITLD+LY, p<0.05; RPP=5212±1955 mmHg*beats/min in ITLD+LY vs.1186±563 mmHg*beats/min in ITLD+Stattic, p<0.05). The infarct size was also larger when compared to Intralipid alone (32.8±3.1% in ITLD+LY vs. 21.7±2.6% in ITLD, p<0.05), but lower than ITLD+Stattic group (32.8±3.1% in ITLD+LY vs 47.9±2.5%, p<0.05). In conclusion, Intralipid protects the late pregnant heart against I/R injury via the STAT3 rather than the PI3K signaling pathway.
-
abstract 215 Intralipid protects the heart in late pregnancy against ischemia reperfusion injury via stat3 signaling pathway
Circulation Research, 2013Co-Authors: Mansoureh EghbaliAbstract:We have recently reported that the hearts of late pregnant (LP) mice are more prone to ischemia/reperfusion (I/R) injury compared to non pregnant mice. We also found that Intralipid, a fat emulsion commonly used for parenteral nutrition, protects the male rodent heart against I/R injury if administrated during reperfusion. The activation of the survivor activating factor enhancement (SAFE) pathway, which includes the activation of the transcription factor signal transducer and activator of transcription-3 (STAT3), has recently been highlighted in cardioprotection. Here we explored the therapeutic potential of Intralipid in the protection of LP mouse hearts against I/R injury as well as the involvement of STAT3 signaling pathway. Isolated LP mouse hearts were subjected to 20 min ischemia followed by reperfusion with i) Krebs Henseleit buffer (CTRL group), ii) 1% Intralipid (ITLD group) or iii) ITLD+STAT3 inhibitor Stattic (20 µM, Stattic group). The duration of reperfusion was 40 min for heart functional measurements and infarct size assessment. Postischemic administration of Intralipid significantly improved the cardiac function of LP mice after ischemia. The rate pressure product (RPP) at the end of reperfusion was improved from 1617±287mmHg*beats/min (n=6) in CTRL to 11556±784 mmHg*beats/min (n=5) in the ITLD group. The infarct size was also significantly reduced by postischemic administration of Intralipid to 17±2% (n=5) from 59±5%(n=6) in CTRL (p
-
Intralipid a clinically safe compound protects the heart against ischemia reperfusion injury more efficiently than cyclosporine a
Anesthesiology, 2012Co-Authors: Andrea Iorga, Salil Sharma, Jiyoun Youn, Rod Partownavid, Soban Umar, Hua Cai, Siamak Rahman, Mansoureh EghbaliAbstract:Background We have recently shown that post-ischemic administration of Intralipid protects the heart against ischemia/reperfusion injury. Here we compared the cardioprotective effects of Intralipid with cyclosporine-A, a potent inhibitor of the mitochondrial permeability transition pore opening.
-
phosphorylation of gsk 3β mediates Intralipid induced cardioprotection against ischemia reperfusion injury
Anesthesiology, 2011Co-Authors: Siamak Rahman, Andrea Iorga, Soban Umar, Jean C Bopassa, Parisa Partownavid, Mansoureh EghbaliAbstract:Background Intralipid, a brand name for the first safe fat emulsion for human use, has been shown to be cardioprotective. However, the mechanism of this protection is not known. Here we investigated the molecular mechanism(s) of Intralipid-induced cardioprotection against ischemia/reperfusion injury, particularly the role of GSK-3β and mitochondiral permeability transition pore in this protective action.
Jesper B Birk - One of the best experts on this subject based on the ideXlab platform.
-
exercise alleviates lipid induced insulin resistance in human skeletal muscle signaling interaction at the level of tbc1 domain family member 4
Diabetes, 2012Co-Authors: Christian Pehmoller, Louise D Hoeg, Kim A Sjoberg, Jesper B Birk, Nina Brandt, Laurie J Goodyear, Bente Kiens, Erik A Richter, Jorgen F P WojtaszewskiAbstract:Excess lipid availability causes insulin resistance. We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle. In eight healthy young male subjects, 1 h of one-legged knee-extensor exercise was followed by 7 h of saline or Intralipid infusion. During the last 2 h, a hyperinsulinemic-euglycemic clamp was performed. Femoral catheterization and analysis of biopsy specimens enabled measurements of leg substrate balance and muscle signaling. Each subject underwent two experimental trials, differing only by saline or Intralipid infusion. Glucose infusion rate and leg glucose uptake was decreased by Intralipid. Insulin-stimulated glucose uptake was higher in the prior exercised leg in the saline and the lipid trials. In the lipid trial, prior exercise normalized insulin-stimulated glucose uptake to the level observed in the resting control leg in the saline trial. Insulin increased phosphorylation of TBC1D1/4. Whereas prior exercise enhanced TBC1D4 phosphorylation on all investigated sites compared with the rested leg, Intralipid impaired TBC1D4 S341 phosphorylation compared with the control trial. Intralipid enhanced pyruvate dehydrogenase (PDH) phosphorylation and lactate release. Prior exercise led to higher PDH phosphorylation and activation of glycogen synthase compared with resting control. In conclusion, lipid-induced insulin resistance in skeletal muscle was associated with impaired TBC1D4 S341 and elevated PDH phosphorylation. The prophylactic effect of exercise on lipid-induced insulin resistance may involve augmented TBC1D4 signaling and glycogen synthase activation.
-
lipid induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling
Diabetes, 2011Co-Authors: Louise D Hoeg, Kim A Sjoberg, Jacob Jeppesen, Thomas E Jensen, Christian Frosig, Jesper B Birk, Bruno Bisiani, Natalie Hiscock, Henriette Pilegaard, Jorgen F P WojtaszewskiAbstract:OBJECTIVE We have previously shown that overnight fasted women have higher insulin-stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism than men. We therefore hypothesized that women would be less prone to lipid-induced insulin resistance. RESEARCH DESIGN AND METHODS Insulin sensitivity of whole-body and leg glucose disposal was studied in 16 young well-matched healthy men and women infused with Intralipid or saline for 7 h. Muscle biopsies were obtained before and during a euglycemic-hyperinsulinemic clamp (1.42 mU · kg−1 · min−1). RESULTS Intralipid infusion reduced whole-body glucose infusion rate by 26% in women and 38% in men ( P < 0.05), and insulin-stimulated leg glucose uptake was reduced significantly less in women (45%) than men (60%) after Intralipid infusion. Hepatic glucose production was decreased during the clamp similarly in women and men irrespective of Intralipid infusion. Intralipid did not impair insulin or AMPK signaling in muscle and subcutaneous fat, did not cause accumulation of muscle lipid intermediates, and did not impair insulin-stimulated glycogen synthase activity in muscle or increase plasma concentrations of inflammatory cytokines. In vitro glucose transport in giant sarcolemmal vesicles was not decreased by acute exposure to fatty acids. Leg lactate release was increased and respiratory exchange ratio was decreased by Intralipid. CONCLUSIONS Intralipid infusion causes less insulin resistance of muscle glucose uptake in women than in men. This insulin resistance is not due to decreased canonical insulin signaling, accumulation of lipid intermediates, inflammation, or direct inhibition of GLUT activity. Rather, a higher leg lactate release and lower glucose oxidation with Intralipid infusion may suggest a metabolic feedback regulation of glucose metabolism.
-
pdh e1α dephosphorylation and activation in human skeletal muscle during exercise effect of Intralipid infusion
Diabetes, 2006Co-Authors: Henriette Pilegaard, Jesper B Birk, Massimo Sacchetti, Marina Mourtzakis, Graham D Hardie, Greg Stewart, Darrell P Neufer, Bengt Saltin, Gerrit Van Hall, Jorgen F P WojtaszewskiAbstract:To investigate pyruvate dehydrogenase (PDH)-E1α subunit phosphorylation and whether free fatty acids (FFAs) regulate PDH activity, seven subjects completed two trials: saline (control) and Intralipid/heparin (Intralipid). Each infusion trial consisted of a 4-h rest followed by a 3-h two-legged knee extensor exercise at moderate intensity. During the 4-h resting period, activity of PDH in the active form (PDHa) did not change in either trial, yet phosphorylation of PDH-E1α site 1 (PDH-P1) and site 2 (PDH-P2) was elevated in the Intralipid compared with the control trial. PDHa activity increased during exercise similarly in the two trials. After 3 h of exercise, PDHa activity remained elevated in the Intralipid trial but returned to resting levels in the control trial. Accordingly, in both trials PDH-P1 and PDH-P2 decreased during exercise, and the decrease was more marked during Intralipid infusion. Phosphorylation had returned to resting levels at 3 h of exercise only in the control trial. Thus, an inverse association between PDH-E1α phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1α phosphorylation, but exercise overrules this effect of FFA on PDH-E1α phosphorylation leading to even greater dephosphorylation during exercise with Intralipid infusion than with saline.
Louise D Hoeg - One of the best experts on this subject based on the ideXlab platform.
-
exercise alleviates lipid induced insulin resistance in human skeletal muscle signaling interaction at the level of tbc1 domain family member 4
Diabetes, 2012Co-Authors: Christian Pehmoller, Louise D Hoeg, Kim A Sjoberg, Jesper B Birk, Nina Brandt, Laurie J Goodyear, Bente Kiens, Erik A Richter, Jorgen F P WojtaszewskiAbstract:Excess lipid availability causes insulin resistance. We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle. In eight healthy young male subjects, 1 h of one-legged knee-extensor exercise was followed by 7 h of saline or Intralipid infusion. During the last 2 h, a hyperinsulinemic-euglycemic clamp was performed. Femoral catheterization and analysis of biopsy specimens enabled measurements of leg substrate balance and muscle signaling. Each subject underwent two experimental trials, differing only by saline or Intralipid infusion. Glucose infusion rate and leg glucose uptake was decreased by Intralipid. Insulin-stimulated glucose uptake was higher in the prior exercised leg in the saline and the lipid trials. In the lipid trial, prior exercise normalized insulin-stimulated glucose uptake to the level observed in the resting control leg in the saline trial. Insulin increased phosphorylation of TBC1D1/4. Whereas prior exercise enhanced TBC1D4 phosphorylation on all investigated sites compared with the rested leg, Intralipid impaired TBC1D4 S341 phosphorylation compared with the control trial. Intralipid enhanced pyruvate dehydrogenase (PDH) phosphorylation and lactate release. Prior exercise led to higher PDH phosphorylation and activation of glycogen synthase compared with resting control. In conclusion, lipid-induced insulin resistance in skeletal muscle was associated with impaired TBC1D4 S341 and elevated PDH phosphorylation. The prophylactic effect of exercise on lipid-induced insulin resistance may involve augmented TBC1D4 signaling and glycogen synthase activation.
-
lipid induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling
Diabetes, 2011Co-Authors: Louise D Hoeg, Kim A Sjoberg, Jacob Jeppesen, Thomas E Jensen, Christian Frosig, Jesper B Birk, Bruno Bisiani, Natalie Hiscock, Henriette Pilegaard, Jorgen F P WojtaszewskiAbstract:OBJECTIVE We have previously shown that overnight fasted women have higher insulin-stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism than men. We therefore hypothesized that women would be less prone to lipid-induced insulin resistance. RESEARCH DESIGN AND METHODS Insulin sensitivity of whole-body and leg glucose disposal was studied in 16 young well-matched healthy men and women infused with Intralipid or saline for 7 h. Muscle biopsies were obtained before and during a euglycemic-hyperinsulinemic clamp (1.42 mU · kg−1 · min−1). RESULTS Intralipid infusion reduced whole-body glucose infusion rate by 26% in women and 38% in men ( P < 0.05), and insulin-stimulated leg glucose uptake was reduced significantly less in women (45%) than men (60%) after Intralipid infusion. Hepatic glucose production was decreased during the clamp similarly in women and men irrespective of Intralipid infusion. Intralipid did not impair insulin or AMPK signaling in muscle and subcutaneous fat, did not cause accumulation of muscle lipid intermediates, and did not impair insulin-stimulated glycogen synthase activity in muscle or increase plasma concentrations of inflammatory cytokines. In vitro glucose transport in giant sarcolemmal vesicles was not decreased by acute exposure to fatty acids. Leg lactate release was increased and respiratory exchange ratio was decreased by Intralipid. CONCLUSIONS Intralipid infusion causes less insulin resistance of muscle glucose uptake in women than in men. This insulin resistance is not due to decreased canonical insulin signaling, accumulation of lipid intermediates, inflammation, or direct inhibition of GLUT activity. Rather, a higher leg lactate release and lower glucose oxidation with Intralipid infusion may suggest a metabolic feedback regulation of glucose metabolism.
Kim A Sjoberg - One of the best experts on this subject based on the ideXlab platform.
-
exercise alleviates lipid induced insulin resistance in human skeletal muscle signaling interaction at the level of tbc1 domain family member 4
Diabetes, 2012Co-Authors: Christian Pehmoller, Louise D Hoeg, Kim A Sjoberg, Jesper B Birk, Nina Brandt, Laurie J Goodyear, Bente Kiens, Erik A Richter, Jorgen F P WojtaszewskiAbstract:Excess lipid availability causes insulin resistance. We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle. In eight healthy young male subjects, 1 h of one-legged knee-extensor exercise was followed by 7 h of saline or Intralipid infusion. During the last 2 h, a hyperinsulinemic-euglycemic clamp was performed. Femoral catheterization and analysis of biopsy specimens enabled measurements of leg substrate balance and muscle signaling. Each subject underwent two experimental trials, differing only by saline or Intralipid infusion. Glucose infusion rate and leg glucose uptake was decreased by Intralipid. Insulin-stimulated glucose uptake was higher in the prior exercised leg in the saline and the lipid trials. In the lipid trial, prior exercise normalized insulin-stimulated glucose uptake to the level observed in the resting control leg in the saline trial. Insulin increased phosphorylation of TBC1D1/4. Whereas prior exercise enhanced TBC1D4 phosphorylation on all investigated sites compared with the rested leg, Intralipid impaired TBC1D4 S341 phosphorylation compared with the control trial. Intralipid enhanced pyruvate dehydrogenase (PDH) phosphorylation and lactate release. Prior exercise led to higher PDH phosphorylation and activation of glycogen synthase compared with resting control. In conclusion, lipid-induced insulin resistance in skeletal muscle was associated with impaired TBC1D4 S341 and elevated PDH phosphorylation. The prophylactic effect of exercise on lipid-induced insulin resistance may involve augmented TBC1D4 signaling and glycogen synthase activation.
-
lipid induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling
Diabetes, 2011Co-Authors: Louise D Hoeg, Kim A Sjoberg, Jacob Jeppesen, Thomas E Jensen, Christian Frosig, Jesper B Birk, Bruno Bisiani, Natalie Hiscock, Henriette Pilegaard, Jorgen F P WojtaszewskiAbstract:OBJECTIVE We have previously shown that overnight fasted women have higher insulin-stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism than men. We therefore hypothesized that women would be less prone to lipid-induced insulin resistance. RESEARCH DESIGN AND METHODS Insulin sensitivity of whole-body and leg glucose disposal was studied in 16 young well-matched healthy men and women infused with Intralipid or saline for 7 h. Muscle biopsies were obtained before and during a euglycemic-hyperinsulinemic clamp (1.42 mU · kg−1 · min−1). RESULTS Intralipid infusion reduced whole-body glucose infusion rate by 26% in women and 38% in men ( P < 0.05), and insulin-stimulated leg glucose uptake was reduced significantly less in women (45%) than men (60%) after Intralipid infusion. Hepatic glucose production was decreased during the clamp similarly in women and men irrespective of Intralipid infusion. Intralipid did not impair insulin or AMPK signaling in muscle and subcutaneous fat, did not cause accumulation of muscle lipid intermediates, and did not impair insulin-stimulated glycogen synthase activity in muscle or increase plasma concentrations of inflammatory cytokines. In vitro glucose transport in giant sarcolemmal vesicles was not decreased by acute exposure to fatty acids. Leg lactate release was increased and respiratory exchange ratio was decreased by Intralipid. CONCLUSIONS Intralipid infusion causes less insulin resistance of muscle glucose uptake in women than in men. This insulin resistance is not due to decreased canonical insulin signaling, accumulation of lipid intermediates, inflammation, or direct inhibition of GLUT activity. Rather, a higher leg lactate release and lower glucose oxidation with Intralipid infusion may suggest a metabolic feedback regulation of glucose metabolism.