Lipid peroxidation in skeletal muscle of obese as compared to endurance‐trained humans: a case of good vs. bad lipids?

Russell, Aaron P.; Gastaldi, Giacomo; Bobbioni-Harsch, Elisabetta; Arboit, Patrizia; Gobelet, Charles; Dériaz, Olivier; Golay, Alain; Witztum, Joseph L.; Giacobino, Jean‐Paul

doi:10.1016/s0014-5793(03)00875-5

Cited by 139 publications

(140 citation statements)

References 13 publications

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“…As elevated IMTG accretion in type 2 diabetic patients is the result of a structural imbalance between NEFA uptake, IMTG deposition and its subsequent mobilisation and/or oxidation [21][22][23], it has been suggested that an elevated IMTG turnover rate can prevent excessive accumulation of intramyocellular FA metabolites [9, 10, 13-16, 44, 45] and/or reduce the degree of intramyocellular lipid peroxidation [17]. In agreement, interventions known to Fig.…”

Section: Discussionmentioning

confidence: 66%

“…More recent insights from various lipid infusion studies have led to an alternative mechanism [9][10][11][12][13]. The latter suggests that elevated NEFA delivery and/or impaired FA oxidation result in intramyocellular accumulation of triacylglycerol (TG) and FA metabolites (such as fatty acyl-CoA, ceramides and diacylglycerol), which induce defects in the insulin signalling cascade, causing skeletal muscle insulin resistance [9,10,[13][14][15][16][17]. Insulin resistance can subsequently lead to development of the hyperglycaemic and/or hyperinsulinaemic state that is associated with type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

“…It has been speculated that an elevated IMTG utilisation rate will prevent excess accumulation of intramyocellular TG and/or FA (metabolites). In addition, a greater IMTG turnover rate may reduce the degree of intramyocellular lipid peroxidation [17], due to a decreased residence time of the lipid deposits. The turnover of the IMTG pool should, therefore, form a major therapeutic target in the prevention and/or treatment of skeletal muscle insulin resistance, and interventions should be developed that stimulate IMTG use [24].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients

et al. 2005

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Aims/hypothesis: In the present study, we investigated the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use in type 2 diabetic patients. Materials and methods: We studied ten type 2 diabetic patients under the following conditions:(1) at rest; (2) during 60 min of cycling exercise at 50% of maximal workload capacity and subsequent recovery. Studies were done under normal, fasting conditions (control trial: CON) and following administration of a nicotinic acid analogue (low plasma non-esterified fatty acid trial: LFA). Continuous [U-13 C]palmitate and [6,6 -2 H 2 ]glucose infusions were applied to quantify plasma NEFA and glucose oxidation rates, and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in lipid and glycogen content specific to muscle fibre type. Results: Following administration of the nicotinic acid analogue (Acipimox), the plasma NEFA rate of appearance was effectively reduced, resulting in lower NEFA concentrations in the LFA trial (p<0.001). Plasma NEFA oxidation rates were substantially reduced at rest, during exercise and subsequent recovery in the LFA trial.The lower plasma NEFA oxidation rates were compensated by an increase in IMTG and endogenous carbohydrate use (p<0.05). Plasma glucose disposal rates did not differ between trials. In accordance with the tracer data, a greater net decline in type I muscle fibre lipid content was observed following exercise in the LFA trial (p<0.05). Conclusions/interpretation: This study shows that plasma NEFA availability regulates IMTG use, and that adipose tissue lipolytic inhibition, in combination with exercise, could be an effective means of augmenting intramuscular lipid and glycogen use in type 2 diabetic patients in an overnight fasted state.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients

et al. 2005

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“…29 Furthermore, an increase in IMTGs has been shown in insulin-resistant obese and Type 2 diabetics, when compared with lean subjects. 3,9 Goodpaster et al 3 found that the IMTG content, measured using a routine Oil red oil stain, correlated with insulin sensitivity in lean, obese and type 2 diabetic subjects. Perseghin et al 30 reported that IMTG, quantified using magnetic resonance spectroscopy (MRS), in offspring of Type 2 diabetic patients correlated with insulin resistance.…”

Section: Association Between Insulin Resistance and Imtg Contentmentioning

confidence: 99%

Lipotoxicity: the obese and endurance-trained paradox

Russell

2004

Int J Obes

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The potential lipotoxic effect of intramyocellular triglyceride (IMTG) accumulation has been suggested to be a major component in the development of insulin resistance. Increased levels of IMTGs correlate with insulin resistance in both obese and diabetic patients, but this relationship does not exist in endurance trained (ETr) subjects. This may be, in part, related to differences in the gene expression and activities of key enzymes involved in fatty acid transport and oxidation as well as in the perodixation status of the IMTGs in obese/diabetic patients as compared with ETr subjects. Disruptions in fat and lipid homeostasis in skeletal muscle have been shown to activate protein kinase C (PKC), which acts on several downstream signalling pathways, including the insulin and the IkB kinase (IKK)/NFkB signalling pathways. Additionally, an increased peroxidation of IMTGs may reduce insulin sensitivity by increasing TNFa, which is known to increase the expression of suppressor of cytokine signalling proteins (SOCS). A common characteristic observed when activating both PKC and TNFa/SOCS3 is the inhibition of tyrosine phosphorylation of IRS-1 and subsequently an inhibition of its activation of downstream signalling molecules. These may be important players in the development of insulin resistance and understanding their activation and expression in both obese and ETr humans should assist in understanding how and why IMTGs become lipotoxic.

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“…Elevated fatty acid delivery and/or impaired fatty acid oxidation result in net intramyocellular accumulation of triacylglycerol and fatty acid metabolites (such as fatty acyl-CoA, ceramides and diacylglycerol). The latter are likely to induce defects in the insulin signalling cascade, thus causing insulin resistance [4][5][6][7][8][9][10] in skeletal muscle.…”

Section: Introductionmentioning

confidence: 99%

Substrate source utilisation in long-term diagnosed type 2 diabetes patients at rest, and during exercise and subsequent recovery

et al. 2006

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Aims/hypothesis Disturbances in substrate source metabolism and, more particularly, in fatty acid metabolism, play an important role in the aetiology and progression of type 2 diabetes. However, data on substrate source utilisation in type 2 diabetes are inconclusive. Methods [U-13 C]palmitate and [6,6-2 H 2 ]glucose tracers were used to assess plasma NEFA and glucose oxidation rates and to estimate the use of muscle-and/or lipoproteinderived triacylglycerol and muscle glycogen. Subjects were ten male patients who had a long-term (7±1 years) diagnosis of type 2 diabetes and were overweight, and ten matched healthy, male control subjects. Muscle biopsy samples were collected before and after exercise to assess muscle fibre type-specific intramyocellular lipid and glycogen content.

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Lipid peroxidation in skeletal muscle of obese as compared to endurance‐trained humans: a case of good vs. bad lipids?

Cited by 139 publications

References 13 publications

Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients

Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients

Lipotoxicity: the obese and endurance-trained paradox

Substrate source utilisation in long-term diagnosed type 2 diabetes patients at rest, and during exercise and subsequent recovery

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