Biomedical subjects

Lorraine P Turcotte

Publications and source records attributed to Lorraine P Turcotte.

11 recordsLinked to original sources

PubMed2006

Thiazolidinediones enhance skeletal muscle triacylglycerol synthesis while protecting against fatty acid-induced inflammation and insulin resistance.

In the present investigation, we studied the effects of thiazolidinedione (TZD) treatment on insulin-stimulated fatty acid (FA) and glucose kinetics in perfused muscle from high-fat (HF)-fed rats. We tested the hypothesis that TZDs prevent FA-induced insulin resistance by attenuating proinflammatory signaling independently of myocellular lipid levels. Male Wistar rats were assigned to one of three 3-wk dietary groups: control chow fed (CON), 65% HF diet (HFD), or TZD- (troglitazone or rosiglitazone) enriched HF diet (TZD + HFD). TZD treatment led to a significant increase in plasma membrane content of CD36 protein in muscle (red: P = 0.01, and white: P = 0.001) that correlated with increased FA uptake (45%, P = 0.002) and triacylglycerol (TG) synthesis (46%, P = 0.03) during the perfusion. Importantly, whereas HF feeding caused increased basal TG (P = 0.047), diacylglycerol (P = 0.002), and ceramide (P = 0.01) levels, TZD treatment only prevented the increase in muscle ceramide. In contrast, all of the muscle inflammatory markers altered by HF feeding ( upward arrowNIK protein content, P = 0.009; upward arrowIKKbeta activity, P = 0.006; downward arrowIkappaB-alpha protein, P = 0.03; and upward arrowJNK phosphorylation, P = 0.003) were completely normalized by TZD treatment. Consistent with this, HFD-induced decrements in insulin action were also prevented by TZD treatment. Thus our findings support the notion that TZD treatment causes increased FA uptake and TG accumulation in skeletal muscle under insulin-stimulated conditions. Despite this, TZDs suppress the inflammatory response to dietary lipid overload, and it is this mechanism that correlates strongly with insulin sensitivity.

Animals↗

PubMed2006

Regulation of contraction-induced FA uptake and oxidation by AMPK and ERK1/2 is intensity dependent in rodent muscle.

Muscle contraction activates AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK1/2), two signaling molecules involved in the regulation of muscle metabolism. The purpose of this study was to determine whether activation of AMPK and/or ERK1/2 contributes to the regulation of muscle fatty acid (FA) uptake and oxidation in contracting muscle. Rat hindquarters were perfused during rest (R) or electrical stimulation (E) of increasing intensity by manipulating train duration (E1 = 25 ms, E2 = 50 ms, E3 = 100 ms, E4 = 200 ms). For matched FA delivery, FA uptake was significantly greater than R during E1, E2, and E3 (7.8 +/- 0.7 vs. 14.4 +/- 0.3, 16.9 +/- 0.8, 15.2 +/- 0.5 nmol.min(-1).g(-1), respectively, P < 0.05), but not during E4 (8.3 +/- 0.3 nmol.min(-1).g(-1), P > 0.05). FA oxidation was significantly greater than R during E1 and E2 (1.5 +/- 0.1 vs. 2.3 +/- 0.2, 2.5 +/- 0.2 nmol.min(-1).g(-1), P < 0.05) before returning to resting levels for E3 and E4 (1.8 +/- 0.1 and 1.5 +/- 0.2 nmol.min(-1).g(-1), P > 0.05). A positive correlation was found between FA uptake and ERK1/2 phosphorylation from R to E3 (R(2) = 0.55, P < 0.05) and between FA oxidation and ERK1/2 phosphorylation from R to E2 (R(2) = 0.76, P < 0.05), correlations that were not maintained when the data for E4 and E3 and E4, respectively, were included in the analysis (R(2) = 0.04 and R(2) = 0.03, P > 0.05). A positive correlation was also found between FA uptake and FA oxidation and AMPK activity for all exercise intensities (R(2) = 0.57, R(2) = 0.65 respectively, P < 0.05). These results, in combination with previous data from our laboratory, suggest that ERK1/2 and AMPK are the predominant signaling molecules regulating FA uptake and oxidation during low- to moderate-intensity muscle contraction and during moderate- to high-intensity muscle contraction, respectively.

AMP-Activated Protein Kinases↗

PubMed2005

Short-term leptin treatment increases fatty acids uptake and oxidation in muscle of high fat-fed rats.

The purpose of this study was to measure the effects of short-term (10 days) leptin treatment on insulin sensitivity as it pertains to fatty acid (FA) uptake, oxidation, and muscle triglyceride (mTG) synthesis in animals that have been administered a high-fat (HF) diet for 3 months. Male Wistar rats were randomly assigned to 1 of 4 groups. One group was fed a control diet (CON) and 3 groups were fed a HF diet. The HF and HF-leptin (HF-LEP) groups were fed the HF diet ad libitum and the amount of food eaten by the HF-pair fed (HF-P) group was equal to that of the HF-LEP group. At the end of the dietary period, rats were injected daily either with saline (CON, HF, HF-P) or with leptin (HF-LEP; 10 mg.kg-1.d-1) for 10 days before hindlimb perfusion. The perfusate contained 600 micromol/L palmitate traced with [14C]palmitate, 9 mmol/L glucose, and 100 microU/mL insulin. As dictated by the protocol, energy expenditure was not significantly different (P>.05) between HF-LEP and HF-P. Palmitate uptake and oxidation as well as mTG synthesis were greater (P<.05) in HF (9.8+/-0.3, 2.0+/-0.1, and 1.9+/-0.2 nmol.min-1.g-1) than in CON (8.0+/-0.4, 1.4+/-0.1, and 1.1+/-0.1 nmol.min-1.g-1) and this was associated with higher levels of mTG in HF. Palmitate uptake and oxidation were higher (P<.05) in HF-LEP (10.3+/-0.6 and 2.0+/-0.1 nmol.min-1.g-1) than in HF-P (8.3+/-0.5 and 1.5+/-0.2 nmol.min-1.g-1, P<.05), but mTG synthesis and mTG levels were not changed significantly by leptin treatment (P>.05). High-fat feeding decreased glucose uptake by 41% when compared with CON (2.4+/-0.4 vs 4.1+/-0.4 micromol.h-1.g-1; P<.05) but pair feeding alone (4.7+/-0.4 micromol.h-1.g-1) or leptin treatment (3.8+/-0.3 micromol.h-1.g-1) similarly prevented the HF diet-induced decrease in glucose uptake. These data indicate that short-term leptin treatment in HF-fed rats alters muscle FA metabolism by increasing FA uptake and oxidation relative to pair feeding alone. This results in a decrease in the FA esterification-oxidation ratio.

Animals↗

PubMed2005

Brief food restriction in old animals decreases triglyceride content and insulin-stimulated triglyceride synthesis.

To determine the effects of brief food restriction on fatty acid (FA) metabolism in old muscle, hind limbs of 24-month F344/BN rats fed either ad libitum (AL) or 60% food restricted (FR) for 28 days were perfused under hyperglycemic-hyperinsulinemic conditions. Basal glucose and insulin levels were significantly lower (p<.05) in FR rats. Although palmitate uptake was not affected by food restriction, palmitate oxidation was 49% lower (2.2+/-0.3 vs 4.3+/-0.7 nmol . g-1 . min-1, p<.05) in FR versus AL animals, respectively. Compared to AL animals, FR animals had 25%-43% (p<.05) lower muscle triglyceride (TG) levels and hyperinsulinemic TG synthesis rates. Higher glucose uptake rates occurred in FR rats (p<.05). In conclusion, our results indicate that brief food restriction in old animals improves insulin sensitivity as it pertains to both glucose uptake and FA oxidation. Together with the decrease in nonoxidative FA disposal, the decreased FA oxidation under hyperinsulinemic conditions may significantly contribute to food restriction-induced reduction in muscle TG.

Aging↗

PubMed2004

AMPK activation is not critical in the regulation of muscle FA uptake and oxidation during low-intensity muscle contraction.

To determine the role of AMP-activated protein kinase (AMPK) activation on the regulation of fatty acid (FA) uptake and oxidation, we perfused rat hindquarters with 6 mM glucose, 10 microU/ml insulin, 550 microM palmitate, and [14C]palmitate during rest (R) or electrical stimulation (ES), inducing low-intensity (0.1 Hz) muscle contraction either with or without 2 mM 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). AICAR treatment significantly increased glucose and FA uptake during R (P < 0.05) but had no effect on either variable during ES (P > 0.05). AICAR treatment significantly increased total FA oxidation (P < 0.05) during both R (0.38 +/- 0.11 vs. 0.89 +/- 0.1 nmol x min(-1) x g(-1)) and ES (0.73 +/- 0.11 vs. 2.01 +/- 0.1 nmol x min(-1) x g(-1)), which was paralleled in both conditions by a significant increase and significant decrease in AMPK and acetyl-CoA carboxylase (ACC) activity, respectively (P < 0.05). Low-intensity muscle contraction increased glucose uptake, FA uptake, and total FA oxidation (P < 0.05) despite no change in AMPK (950.5 +/- 35.9 vs. 1,067.7 +/- 58.8 nmol x min(-1) x g(-1)) or ACC (51.2 +/- 6.7 vs. 55.7 +/- 2.0 nmol x min(-1) x g(-1)) activity from R to ES (P > 0.05). When contraction and AICAR treatment were combined, the AICAR-induced increase in AMPK activity (34%) did not account for the synergistic increase in FA oxidation (175%) observed under similar conditions. These results suggest that while AMPK-dependent mechanisms may regulate FA uptake and FA oxidation at rest, AMPK-independent mechanisms predominate during low-intensity muscle contraction.

AMP-Activated Protein Kinases↗

PubMed2003

Aging is associated with elevated muscle triglyceride content and increased insulin-stimulated fatty acid uptake.

The purpose of the present study was to examine the utilization of fatty acids (FA) and muscle substrates by skeletal muscle in young, middle-aged, and old adult rats under hyperglycemic and hyperinsulinemic conditions. Male Fischer 344 x Brown Norway rats aged 5, 15, or 24 mo underwent hindlimb perfusion with a medium of 20 mM glucose, 1 mM palmitate, 1,000 microU/ml insulin, [1-14C]palmitate, and [3-3H]glucose. Glucose uptake and palmitate delivery were similar among age groups. Palmitate uptake and oxidation as well as muscle protein concentration of fatty acid translocase (FAT/CD36) and plasma membrane fatty acid-binding protein (FABPPM) were significantly increased (P < or = 0.05) in 24- vs. 5- and 15-mo-old animals. Compared with 5- and 15-mo-old animals, pre- and postperfusion muscle triglyceride (TG) levels were significantly (P < 0.05) elevated 72-145% in red and 112-129% in white muscles of 24-mo-old animals. Palmitate uptake was associated with total preperfusion TG concentration (r2 = 0.27, P < 0.05) and total TG synthesis rate (r2 = 0.68, P < 0.05). These results indicate that, under insulin-stimulated conditions, FA uptake is significantly increased in old animals, which is associated with increased rates of TG synthesis and may contribute to the accumulation of TG in muscle of old animals.

Aging↗

PubMed2003

Mitochondria: biogenesis, structure, and function--symposium introduction.

During the past three to four decades, a significant amount of data was collected to reinforce the notion that mitochondrial function is irrevocably linked to mitochondrial structure. Indeed, data from numerous studies have revealed several salient points of mitochondrial biology that include the following: 1). mitochondria exist as a reticulum rather than as single entities, 2). different mitochondrial populations identified by their cellular location are characterized by different structural and functional characteristics, and 3). muscle mitochondrial respiratory capacity readily adapts to changes in muscle use and disuse by adjusting tissue metabolic capacity to match functional demands. More recently, research in the area of mitochondrial biology has focused on uncovering 1). the cellular signals responsible for the control of mitochondrial biogenesis via coordinate regulation of nuclear and mitochondrial gene expression, 2). the mechanisms by which mitochondrial respiration is regulated, and 3). the role of mitochondria in apoptotic cell death. The most current knowledge in these areas of mitochondrial biology will be addressed in the following symposium papers.

Adaptation, Physiological↗

PubMed2002

Impaired fatty acid oxidation in muscle of aging rats perfused under basal conditions.

The purpose of the present study was to examine the utilization of fatty acids (FA) and muscle substrates by skeletal muscle in young, middle-aged, and old adult rats under conditions of euglycemia with low insulin levels. Male Fischer 344 x Brown Norway rats aged 5, 15, or 24 mo underwent hindlimb perfusion with a medium of 8 mM glucose, 1 mM palmitate, 25 microU/ml insulin, [1-(14)C]palmitate, and [3-(3)H]glucose. Glucose and palmitate uptake were similar among age groups. The percent and total palmitate oxidized (nmol.min(-1).g(-1)) were 30-36 and 41-49% lower (P < 0.05) in 15-mo- and 24-mo-old than in 5-mo-old animals. Compared with 5-mo- and 15-mo-old animals, pre- and postperfusion muscle triglyceride (TG) levels were significantly (P < 0.05) elevated 91-305% in red and 118-219% in white muscles of 24-mo-old animals. Fatty acid-binding protein content was 40-64% higher (P < 0.05) in 24-mo- than in 5-mo- or 15-mo-old animals. In red muscle, hormone-sensitive lipase (HSL) content was 28% lower (P < 0.05) in 24-mo- than in 5-mo-old animals. These results indicate that, under euglycemic conditions in the presence of low insulin levels, the reduction in FA disposal to oxidation and the decrease in HSL content may contribute to the accumulation of TG in muscle of old animals.

Aging↗

PubMed2002

High carbohydrate availability increases LCFA uptake and decreases LCFA oxidation in perfused muscle.

To determine whether changes in long-chain fatty acid (LCFA) oxidative metabolism induced by elevated intracellular carbohydrate availability are due to changes in LCFA uptake or in mitochondrial transport capacity, rat hindquarters were perfused with 500 microM palmitate and [1-14C]palmitate or [1-14C]octanoate as well as with either low (LG) or high (HG) carbohydrate availability. Glucose uptake was higher in the HG vs. LG group (23.6 +/- 1.5 vs 4.7 +/- 0.9 micromol x g(-1) x h(-1), P < 0.05). Palmitate delivery was not significantly different between groups and averaged 97.1 +/- 4.6 nmol x min(-1) x g(-1) (P > 0.05). Fractional and total palmitate uptake values were 60% higher (P < 0.05) in the HG (0.125 +/- 0.012 and 7.4 +/- 1.2 nmol x min(-1) x g(-1)) vs. LG (0.079 +/- 0.009 and 11.8 +/- 1.5 nmol x min(-1) x g(-1)) group. Values of percent and total palmitate oxidized were significantly lower (P < 0.05) in the HG (9.1 +/- 1.1% and 1.31 +/- 0.16 nmol x min(-1) x g(-1)) vs. LG (23.4 +/- 5.2% and 0.76 +/- 0.08 nmol x min(-1) x g(-1)) group. Conversely, values of fractional uptake and percent oxidation of octanoate were not significantly different between groups (P > 0.05). Malonyl-CoA levels were inversely correlated with LCFA oxidation (P < 0.05). These results demonstrate that high carbohydrate availability in muscle is associated with a decrease in LCFA oxidation that is not due to a parallel decrease in LCFA uptake; rather, the decrease in LCFA oxidation could be due to malonyl-CoA inhibition of mitochondrial LCFA transport.

Animals↗

PubMed2002

Insulin fails to alter plasma LCFA metabolism in muscle perfused at similar glucose uptake.

Insulin has been shown to alter long-chain fatty acid (LCFA) metabolism and malonyl-CoA production in muscle. However, these alterations may have been induced, in part, by the accompanying insulin-induced changes in glucose uptake. Thus, to determine the effects of insulin on LCFA metabolism independently of changes in glucose uptake, rat hindquarters were perfused with 600 microM palmitate and [1-(14)C]palmitate and with either 20 mM glucose and no insulin (G) or 6 mM glucose and 250 microU/ml of insulin (I). As dictated by our protocol, glucose uptake was not significantly different between the G and I groups (10.3 +/- 0.6 vs. 11.0 +/- 0.5 micromol x g(-1) x h(-1); P > 0.05). Total palmitate uptake and oxidation were not significantly different (P > 0.05) between the G (10.1 +/- 1.0 and 0.8 +/- 0.1 nmol x min(-1) x g(-1)) and I (10.2 +/- 0.6 and 1.1 +/- 0.2 nmol. min(-1) x g(-1)) groups. Preperfusion muscle triglyceride and malonyl-CoA levels were not significantly different between the G and I groups and did not change significantly during the perfusion (P > 0.05). Similarly, muscle triglyceride synthesis was not significantly different between groups (P > 0.05). These results demonstrate that the presence of insulin under conditions of similar glucose uptake does not alter LCFA metabolism and suggest that cellular mechanisms induced by carbohydrate availability, but independent of insulin, may be important in the regulation of muscle LCFA metabolism.

Animals↗

PubMed2002

Brief food restriction increases FA oxidation and glycogen synthesis under insulin-stimulated conditions.

To determine the effects of brief food restriction on fatty acid (FA) metabolism, hindlimbs of F344/BN rats fed either ad libitum (AL) or food restricted (FR) to 60% of baseline food intake for 28 days were perfused under hyperglycemic-hyperinsulinemic conditions (20 mM glucose, 1 mM palmitate, 1,000 microU/ml insulin, [3-(3)H]glucose, and [1-(14)C]palmitate). Basal glucose and insulin levels were significantly lower (P < 0.05) in FR vs. AL rats. Palmitate uptake (34.3 +/- 2.7 vs. 24.5 +/- 3.1 nmol/g/min) and oxidation (3.8 +/- 0.2 vs. 2.7 +/- 0.3 nmol.g(-1).min(-1)) were significantly higher (P < 0.05) in FR vs. AL rats, respectively. Glucose uptake was increased in FR rats and was accompanied by significant increases in red and white gastrocnemius glycogen synthesis, indicating an improvement in insulin sensitivity. Although muscle triglyceride (TG) levels were not significantly different between groups, glucose uptake and total preperfusion TG concentration were negatively correlated (r(2) = 0.27, P < 0.05). In conclusion, our results show that under hyperglycemic-hyperinsulinemic conditions, brief FR resulted in an increase in FA oxidative disposal that may contribute to the improvement in insulin sensitivity.

Animals↗