scholarly journals Relative Contribution of Intramyocellular Lipid to Whole-Body Fat Oxidation Is Reduced With Age but Subsarcolemmal Lipid Accumulation and Insulin Resistance Are Only Associated With Overweight Individuals

Diabetes ◽  
2016 ◽  
Vol 65 (4) ◽  
pp. 840-850 ◽  
Author(s):  
Carolyn Chee ◽  
Chris E. Shannon ◽  
Aisling Burns ◽  
Anna L. Selby ◽  
Daniel Wilkinson ◽  
...  
2018 ◽  
Vol 314 (3) ◽  
pp. R468-R477 ◽  
Author(s):  
Bailey Peck ◽  
Josh Huot ◽  
Tim Renzi ◽  
Susan Arthur ◽  
Michael J. Turner ◽  
...  

Protein kinase C-θ (PKC-θ) is a lipid-sensitive molecule associated with lipid-induced insulin resistance in skeletal muscle. Rodent models have not cohesively supported that PKC-θ impairs insulin responsiveness in skeletal muscle. The purpose of this study was to generate mice that lack PKC-θ in skeletal muscle and determine how lipid accumulation and insulin responsiveness are affected in that tissue. Mice lacking PKC-θ in skeletal muscle (SkMPKCθKO) and controls (SkMPKCθWT) were placed on a regular diet (RD) or high-fat diet (HFD) for 15 wk, followed by determination of food intake, fasting glucose levels, lipid accumulation, and insulin responsiveness. There were no differences between SkMPKCθWTand SkMPKCθKOmice on a RD. SkMPKCθKOmice on a HFD gained less weight from 10 through 15 wk of dietary intervention ( P < 0.05). This was likely due to less caloric consumption ( P = 0.0183) and fewer calories from fat ( P < 0.001) compared with SkMPKCθWTmice on a HFD. Intramyocellular lipid accumulation ( P < 0.0001), fatty acid binding protein 4, and TNF-α mRNA levels ( P < 0.05) were markedly reduced in SkMPKCθKOcompared with SkMPKCθWTmice on a HFD. As a result, fasting hyperglycemia was mitigated and insulin responsiveness, as indicated by Akt phosphorylation, was maintained in SkMPKCθKOon a HFD. Liver lipid accumulation was not affected by genotype, suggesting the deletion of PKC-θ from skeletal muscle has a tissue-specific effect. PKC-θ is a regulator of lipid-induced insulin resistance in skeletal muscle. However, the effects of this mutation may be tissue specific. Further work is warranted to comprehensively evaluated whole body metabolic responses in this model.


2018 ◽  
Vol 28 (12) ◽  
pp. 2494-2504 ◽  
Author(s):  
Sune Dandanell ◽  
Anne-Kristine Meinild-Lundby ◽  
Andreas B. Andersen ◽  
Paul F. Lang ◽  
Laura Oberholzer ◽  
...  

Aging Cell ◽  
2021 ◽  
Vol 20 (2) ◽  
Author(s):  
Carolyn Chee ◽  
Chris E. Shannon ◽  
Aisling Burns ◽  
Anna L. Selby ◽  
Daniel Wilkinson ◽  
...  

2004 ◽  
Vol 287 (1) ◽  
pp. E120-E127 ◽  
Author(s):  
Matthew J. Watt ◽  
Anna G. Holmes ◽  
Gregory R. Steinberg ◽  
Jose L. Mesa ◽  
Bruce E. Kemp ◽  
...  

Intramuscular triacylglycerols (IMTG) are proposed to be an important metabolic substrate for contracting muscle, although this remains controversial. To test the hypothesis that reduced plasma free fatty acid (FFA) availability would increase IMTG degradation during exercise, seven active men cycled for 180 min at 60% peak pulmonary O2 uptake either without (CON) or with (NA) prior ingestion of nicotinic acid to suppress adipose tissue lipolysis. Skeletal muscle and adipose tissue biopsy samples were obtained before and at 90 and 180 min of exercise. NA ingestion decreased ( P < 0.05) plasma FFA at rest and completely suppressed the exercise-induced increase in plasma FFA (180 min: CON, 1.42 ± 0.07; NA, 0.10 ± 0.01 mM). The decreased plasma FFA during NA was associated with decreased ( P < 0.05) adipose tissue hormone-sensitive lipase (HSL) activity (CON: 13.9 ± 2.5, NA: 9.1 ± 3.0 nmol·min−1·mg protein−1). NA ingestion resulted in decreased whole body fat oxidation and increased carbohydrate oxidation. Despite the decreased whole body fat oxidation, net IMTG degradation was greater in NA compared with CON (net change: CON, 2.3 ± 0.8; NA, 6.3 ± 1.2 mmol/kg dry mass). The increased IMTG degradation did not appear to be due to reduced fatty acid esterification, because glycerol 3-phosphate activity was not different between trials and was unaffected by exercise (rest: 0.21 ± 0.07; 180 min: 0.17 ± 0.04 nmol·min−1·mg protein−1). HSL activity was not increased from resting rates during exercise in either trial despite elevated plasma epinephrine, decreased plasma insulin, and increased ERK1/2 phosphorylation. AMP-activated protein kinase (AMPK)α1 activity was not affected by exercise or NA, whereas AMPKα2 activity was increased ( P < 0.05) from rest during exercise in NA and was greater ( P < 0.05) than in CON at 180 min. These data suggest that plasma FFA availability is an important mediator of net IMTG degradation, and in the absence of plasma FFA, IMTG degradation cannot maintain total fat oxidation. These changes in IMTG degradation appear to disassociate, however, from the activity of the key enzymes responsible for synthesis and degradation of this substrate.


2019 ◽  
Vol 126 (6) ◽  
pp. 1563-1571 ◽  
Author(s):  
Jacob Frandsen ◽  
Stine Dahl Vest ◽  
Christian Ritz ◽  
Steen Larsen ◽  
Flemming Dela ◽  
...  

Plasma free fatty acids (FFA) are a major contributor to whole body fat oxidation during exercise. However, the extent to which manipulating plasma FFA concentrations will influence whole body peak fat oxidation rate (PFO) during exercise remains elusive. In this study we aimed to increase plasma FFA concentrations through a combination of fasting and repeated exercise bouts. We hypothesized that an increase in plasma FFA concentration would increase PFO in a dose-dependent manner. Ten healthy young (31 ± 6 yr) (mean ± SD) well-trained (maximal oxygen uptake 65.9 ± 6.1 ml·min−1·kg−1) men performed four graded exercise tests (GXTs) on 1 day. The GXTs were interspersed by 4 h of bed rest. This was conducted either in a fasted state or with the consumption of a standardized carbohydrate-rich meal 3.5 h before each GXT. Fasting and previous GXTs resulted in a gradual increase in PFO from 0.63 ± 0.18 g/min after an overnight fast (10 h) to 0.93 ± 0.17 g/min after ∼22 h of fasting and three previous GXTs. This increase in PFO coincided with an increase in plasma FFA concentrations ( r2 = 0.73, P < 0.0001). Ingestion of a carbohydrate-rich meal 3.5 h before each GXT resulted in unaltered PFO. This was also reflected in unchanged plasma FFA, glucose, and insulin concentrations. In this study we show that plasma FFA availability is closely tied to whole body PFO and that the length of fasting combined with previous exercise are robust stimuli toward increasing plasma FFA concentration, highlighting the importance for preexercise standardization when conducting GXTs measuring substrate oxidation. NEW & NOTEWORTHY We show that peak fat oxidation is increased in close relationship with plasma free fatty acid availability after combined fasting and repeated incremental exercise tests in healthy highly trained men. Therefore it may be argued that whole body fat oxidation rate measured in most cases after an overnight fast indeed does not represent whole body maximal fat oxidation rate but a whole body peak fat oxidation rate within the context of the preexercise standardization obtained in the study design.


Metabolism ◽  
2011 ◽  
Vol 60 (8) ◽  
pp. 1051-1057 ◽  
Author(s):  
Jackson G. Green ◽  
Nathan A. Johnson ◽  
Toos Sachinwalla ◽  
Christopher W. Cunningham ◽  
Martin W. Thompson ◽  
...  

2011 ◽  
Vol 8 (6) ◽  
pp. 820-823 ◽  
Author(s):  
Erik Hemmingsson ◽  
Ulf Ekelund ◽  
Joanna Udden

Background:The impact of walking and bicycling on insulin resistance (IR) in women with abdominal obesity is unclear.Methods:Pooled analysis of data from a randomized trial on physically active commuting (bicycling + walking vs walking only) in women with abdominal obesity [n = 98; age:47.3 ± 7.6 yrs; waist circumference (WC):103.1 ± 7.8 cm]. Bicycling and walking data were collected during 7 consecutive days by trip meters (Trelock FC-410) and pedometers (Yamax digiwalker SW-200) at baseline, 2, 4, and 6 months. Owing to a skew distribution we analyzed bicycling as a binary dummy variable with a 10 km/week cut-off. Fasting serum insulin and homeostatic model assessment – insulin resistance (HOMA-IR) were assessed at baseline and 6 months, as were body mass index (BMI), WC, and dual x-ray absorptiometry (DXA)-assessed % whole-body fat.Results:Increased bicycling by 10 km/wk was associated with reductions in fasting serum insulin at follow-up independent of age, treatment allocation, baseline phenotype, Δ walking, and Δ % body fat (β = −10.9, P = .042), but not HOMA-IR (β = −2.0, P = .13). Increased walking was not associated with fasting serum insulin (P = .33) or HOMA-IR (P = .44) at follow-up, after adjustment for the same covariates and Δ bicycling.Conclusion:Increased bicycling but not walking was associated with reduced insulin levels at follow-up. Bicycling may be more effective than walking for reducing insulin levels in abdominally obese women.


2006 ◽  
Vol 100 (2) ◽  
pp. 609-614 ◽  
Author(s):  
Martin Torriani ◽  
Bijoy J. Thomas ◽  
Robert B. Barlow ◽  
Jamie Librizzi ◽  
Sara Dolan ◽  
...  

The human immunodeficiency virus (HIV)-lipodystrophy syndrome is associated with fat redistribution and metabolic abnormalities, including insulin resistance. Increased intramyocellular lipid (IMCL) concentrations are thought to contribute to insulin resistance, being linked to metabolic and body composition variables. We examined 46 women: HIV infected with fat redistribution ( n = 25), and age- and body mass index-matched HIV-negative controls ( n = 21). IMCL was measured by 1H-magnetic resonance spectroscopy, and body composition was assessed with computed tomography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging. Plasma lipid profile and markers of glucose homeostasis were obtained. IMCL was significantly increased in tibialis anterior [135.0 ± 11.5 vs. 85.1 ± 13.2 institutional units (IU); P = 0.007] and soleus [643.7 ± 61.0 vs. 443.6 ± 47.2 IU, P = 0.017] of HIV-infected subjects compared with controls. Among HIV-infected subjects, calf subcutaneous fat area (17.8 ± 2.3 vs. 35.0 ± 2.5 cm2, P < 0.0001) and extremity fat by DEXA (11.8 ± 1.1 vs. 15.6 ± 1.2 kg, P = 0.024) were reduced, whereas visceral abdominal fat (125.2 ± 11.3 vs. 74.4 ± 12.3 cm2, P = 0.004), triglycerides (131.1 ± 11.0 vs. 66.3 ± 12.3 mg/dl, P = 0.0003), and fasting insulin (10.8 ± 0.9 vs. 7.0 ± 0.9 μIU/ml, P = 0.004) were increased compared with control subjects. Triglycerides ( r = 0.39, P = 0.05) and extremity fat as percentage of whole body fat by DEXA ( r = −0.51, P = 0.01) correlated significantly with IMCL in the HIV but not the control group. Extremity fat (β = −633.53, P = 0.03) remained significantly associated with IMCL among HIV-infected patients, controlling for visceral abdominal fat, abdominal subcutaneous fat, and antiretroviral medications in a regression model. These data demonstrate increased IMCL in HIV-infected women with a mixed lipodystrophy pattern, being most significantly associated with reduced extremity fat. Further studies are necessary to determine the relationship between extremity fat loss and increased IMCL in HIV-infected women.


Sign in / Sign up

Export Citation Format

Share Document