Free fatty acid oxidation by forearm muscle at rest, and evidence for an intramuscular lipid pool in the human forearm.

Dagenais, Gilles R.; Tancredi, Robert G.; Zierler, Kenneth L.

doi:10.1172/jci108486

Cited by 222 publications

(137 citation statements)

References 26 publications

Supporting

Mentioning

125

Contrasting

Order By: Relevance

“…Thus, peripheral hyperinsulinaemia and hyperglycaemia may contribute to the elevated mTG concentrations in our IDDM patients. The disappearance of the difference in mTG content between our patients and healthy subjects during hyperinsulinaemia is in accordance with an intramuscular source of fatty acids with a slow turnover rate [2]. In the current study serum NEFA concentrations were equal in the two groups at the end of insulin infusion.…”

Section: Discussionsupporting

confidence: 82%

“…Most of the fatty acids taken up by resting muscle are not oxidized directly, but enter an intramuscular pool with a slow turnover at rest and are the immediate source of lipid substrate for oxidation [2]. The NEFA taken up by muscle are incorporated to lipid droplets in muscle and 70--90 % of fatty acids entering the muscle are rapidly esterified to triglyceride (TG) [3].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Intramuscular triglyceride content is increased in IDDM

et al. 1998

View full text Add to dashboard Cite

Increased lipid oxidation is related to insulin resistance [1]. Most of the fatty acids taken up by resting muscle are not oxidized directly, but enter an intramuscular pool with a slow turnover at rest and are the immediate source of lipid substrate for oxidation [2]. The NEFA taken up by muscle are incorporated to lipid droplets in muscle and 70--90 % of fatty acids entering the muscle are rapidly esterified to triglyceride (TG) [3]. For example, raising extracellular palmitate increases esterification, but does not increase intramuscular concentration of palmitate [4]. Part of the enhanced lipid oxidation can be derived from intramuscular sources [5].As compared to healthy subjects a sixfold increase of muscle (m) TG in patients with non-insulin-dependent diabetes mellitus [6], and a sevenfold increase in TG content in striated muscle in coronary bypass-operated patients with impaired glucose tolerance [7] have been reported in comparison to control groups. These patient groups are also characterized by insulin resistance. Sustained euglycaemic hyperinsulinaemia Diabetologia (1998) Summary Increased lipid oxidation is related to insulin resistance. Some of the enhanced lipid utilization may be derived from intramuscular sources. We studied muscle triglyceride (mTG) concentration and its relationship to insulin sensitivity in 10 healthy men (age 29 ± 2 years, BMI 23.3 ± 0.6 kg/m 2 ) and 17 men with insulin-dependent diabetes mellitus (IDDM) (age 30 ± 2 years, BMI 22.8 ± 0.5 kg/m 2 , diabetes duration 14 ± 2 years, HbA 1 c 7.7 ± 0.3 %, insulin dose 48 ± 3 U/day). Insulin sensitivity was measured with a 4 h euglycaemic (5 mmol/l) hyperinsulinaemic (1.5 mU or 9 pmol ⋅ kg --1 ⋅ min --1 ) clamp accompanied by indirect calorimetry before and at the end of the insulin infusion. A percutaneous biopsy was performed from m. vastus lateralis for the determination of mTG. At baseline the IDDM patients had higher glucose (10.2 ± 0.9 vs 5.6 ± 0.1 mmol/l, p < 0.001), insulin (40.3 ± 3.2 vs 23.2 ± 4.2 pmol/l, p < 0.01), HDL cholesterol (1.28 ± 0.06 vs 1.04 ± 0.03 mmol/l, p < 0.01) and mTG (32.9 ± 4.6 vs 13.6 ± 2.7 mmol/kg dry weight, p < 0.01) concentrations than the healthy men, respectively. The IDDM patients had lower insulin stimulated whole body total (--25 %, p < 0.001), oxidative (--18 %, p < 0.01) and non-oxidative glucose disposal rates (--43 %, p < 0.001), whereas lipid oxidation rate was higher in the basal state ( + 44 %, p < 0.01) and during hyperinsulinaemia ( + 283 %, p < 0.05). mTG concentrations did not change significantly during the clamp or correlate with insulin stimulated glucose disposal. In healthy men mTG correlated positively with lipid oxidation rate at the end of hyperinsulinaemia (r = 0.75, p < 0.05). In conclusion: 1) IDDM is associated with increased intramuscular TG content. 2) mTG content does not correlate with insulin sensitivity in healthy subjects or patients with IDDM. [Diabetologia (1998) 41: 111--115]

show abstract

Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 99%

Intramuscular triglyceride content is increased in IDDM

et al. 1998

View full text Add to dashboard Cite

show abstract

“…This is in agreement with reports of decreased lipid oxidation in men with very low levels of testosterone, i.e., hypogonadism due to pituitary disease (Birzniece et al 2009). In human skeletal muscle, lipid is the predominate oxidative substrate during fasting, accounting for approximately 80% of oxygen consumption (Dagenais et al 1976). Therefore, the observed effect of testosterone therapy on fuel selection (decrease in RQ) could, in part, be explained by the increase in muscle mass (LBM).…”

Section: Discussionmentioning

confidence: 99%

Testosterone therapy increased muscle mass and lipid oxidation in aging men

Frederiksen

Højlund

Hougaard

et al. 2011

AGE

115

View full text Add to dashboard Cite

The indication for testosterone therapy in aging hypogonadal men without hypothalamic, pituitary, or testicular disease remains to be elucidated. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity, substrate metabolism, body composition, and lipids in aging men with low normal bioavailable testosterone levels using a predefined cutoff level for bioavailable testosterone. A randomized, double-blinded, placebocontrolled study of testosterone treatment (gel) was done on 38 men, aged 60-78 years, with bioavailable testosterone <7.3 nmol/l and a waist circumference >94 cm. Insulin-stimulated glucose disposal (Rd) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry. Lean body mass (LBM) and total fat mass (TFM) were measured by dual x-ray absorptiometry, and serum total testosterone was measured by tandem mass spectrometry. Bioavailable testosterone was calculated. Coefficients (b) represent the placebo-controlled mean effect of intervention. LBM (b=1.9 kg, p=0.003) increased while HDL-cholesterol (b=−0.12 mmol/l, p=0.043) and TFM decreased (b=−1.2 kg, p=0.038) in the testosterone group compared to placebo. Basal lipid oxidation (b=5.65 mg/min/m 2 , p=0.045) increased and basal glucose oxidation (b=−9.71 mg/min/m 2 , p = 0.046) decreased in response to testosterone therapy even when corrected for changes in LBM. No significant changes in insulin-stimulated Rd was observed (b=−0.01mg/min/m 2 , p=0.92). Testosterone therapy increased muscle mass and lipid oxidation in aging men with low normal bioavailable testosterone levels; however, our data did not support an effect of testosterone on whole-body insulin sensitivity using the euglycemic hyperinsulinemic clamp technique.

show abstract

“…While this pool makes up only a small portion of the total intramuscular lipid, it likely plays a critical role in lipid fuel metabolism within muscle. At rest as much as 80% of the fuel burned by muscle is lipid (9). Previous studies have demonstrated that intramuscular TG contributes significantly to the lipid oxidized during exercise (21,46), with electrical stimulation (27,28,45) and with fasting (31).…”

Section: Discussionmentioning

confidence: 99%

“…Intramuscular TG content correlates with insulin resistance (35,47), and with the clearance of TGFA (18). The intramuscular triglyceride pool receives FA from circulating NEFA (9) or from intramuscular FA synthesis. The data presented suggest that circulating TGFA also make a contribution to this pool.…”

Section: Discussionmentioning

confidence: 99%

Trafficking of Dietary Fat in Lean Rats

1995

View full text Add to dashboard Cite

BESSESEN, DANIEL H, CONNIE L RUPP AND ROBERT H ECKEL. Trafficking of dietary fat in lean rats. Obes Res. 1995;3:191-203. Despite increasing interest in the role that fuel partitioning plays in determining body composition, the relative importance of oxidative versus storage pathways in the clearance of dietary fat remains unclear. A widely held view is that the primary destination of chylomicron triglyceride fatty acids (TGFA) is adipose tissue, and the primary source of lipid fuel for skeletal muscle is non-esterified fatty acids (NEFA).An alternate view is that muscle, not adipose tissue, is the primary site of TGFA clearance. This view is supported by estimates of the total lipoprotein lipase content of muscle and adipose tissue. To directly study the partitioning of dietary fat between oxidation and storage, 14C-labeled oleic acid was fed to Sprague Dawley rats and its metabolic fate followed over 30 days. Two hours after ingestion, more than 3.5 times as much label was found in skeletal muscle tissue (2.42 f 0.45 nmols) and C 0 2 (0.25 f 0.01 nmols) than was found in adipose tissue (0.71 f 0.14 nmols). Intramuscular triglyceride was the lipid class most extensively labeled. After skeletal muscle, liver was the next most important site of TGFA clearance. Surprisingly a substantial quantity of label remained associated with the GI tract even 24 hours after ingestion. Between 2 and 10 days following ingestion there was a net decline in the 14C content of muscle, liver and GI tract, associated with a net rise in the 14C content of adipose tissue. These findings demonstrate: 1) the importance of skeletal muscle and liver in whole organism TGFA clearance, 2) the importance of intramuscular partitioning of lipid fuels between direct oxidation and storage as TG, 3) the potentially important role of the GI tract in the delivery of dietary fat to the circulation 10-24 hours following ingestion, and 4) the stability of adipose tissue as a storage site. The complex nature of the tissue-specific clearance of TGFA over time is perhaps better described by the term "trafficking' than by the more commonly used term "partitioning." Future studies of TGFA clearance combined with sampling of relevant tissues over time will provide insight into the specific roles that abnormalities in liver, muscle and adipose tissue TGFA metabolism play in the development of hypertriglyceridemic disorders and states of increased or reduced body weight.

show abstract

Free fatty acid oxidation by forearm muscle at rest, and evidence for an intramuscular lipid pool in the human forearm.

Cited by 222 publications

References 26 publications

Intramuscular triglyceride content is increased in IDDM

Intramuscular triglyceride content is increased in IDDM

Testosterone therapy increased muscle mass and lipid oxidation in aging men

Trafficking of Dietary Fat in Lean Rats

Contact Info

Product

Resources

About