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  • 1
    Online Resource
    Online Resource
    Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise
    Elsevier BV ; 2020
    In:  Cell Vol. 181, No. 7 ( 2020-06), p. 1464-1474
    Details
    In: Cell, Elsevier BV, Vol. 181, No. 7 ( 2020-06), p. 1464-1474
    Type of Medium: Online Resource
    ISSN: 0092-8674
    URL: Article
    DOI: 10.1016/j.cell.2020.06.004
    RVK:
    XA 36269
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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  • 2
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    Early Life Exposure to Maternal Insulin Resistance Has Persistent Effects on Hepatic NAFLD in Juvenile Nonhuman Primates
    American Diabetes Association ; 2014
    In:  Diabetes Vol. 63, No. 8 ( 2014-08-01), p. 2702-2713
    Details
    In: Diabetes, American Diabetes Association, Vol. 63, No. 8 ( 2014-08-01), p. 2702-2713
    Abstract: The origins of nonalcoholic fatty liver disease (NAFLD) may lie in early intrauterine exposures. Here we examined the maternal response to chronic maternal high-fat (HF) diet and the impact of postweaning healthy diet on mechanisms for NAFLD development in juvenile nonhuman primate (NHP) offspring at 1 year of age. Pregnant females on HF diet were segregated as insulin resistant (IR; HF+IR) or insulin sensitive (IS; HF+IS) compared with control (CON)-fed mothers. HF+IR mothers have increased body mass, higher triglycerides, and increased placental cytokines. At weaning, offspring were placed on a CON or HF diet. Only offspring from HF+IR mothers had increased liver triglycerides and upregulated pathways for hepatic de novo lipid synthesis and inflammation that was irreversible upon switching to a healthy diet. These juvenile livers also showed a combination of classical and alternatively activated hepatic macrophages and natural killer T cells, in the absence of obesity or insulin resistance. Our findings suggest that maternal insulin resistance, including elevated triglycerides, insulin, and weight gain, initiates dysregulation of the juvenile hepatic immune system and development of de novo lipogenic pathways that persist in vitro and may be an irreversible “first hit” in the pathogenesis of NAFLD in NHP.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db14-0276
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2014
    detail.hit.zdb_id: 1501252-9
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  • 3
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    Utilization of Mid-Thigh Magnetic Resonance Imaging to Predict Lean Body Mass and Knee Extensor Strength in Obese Adults
    Frontiers Media SA ; 2022
    In:  Frontiers in Rehabilitation Sciences Vol. 3 ( 2022-3-24)
    Details
    In: Frontiers in Rehabilitation Sciences, Frontiers Media SA, Vol. 3 ( 2022-3-24)
    Abstract: To train and test a machine learning model to automatically measure mid-thigh muscle cross-sectional area (CSA) to provide rapid estimation of appendicular lean mass (ALM) and predict knee extensor torque of obese adults. Methods Obese adults [body mass index (BMI) = 30–40 kg/m 2 , age = 30–50 years] were enrolled for this study. Participants received full-body dual-energy X-ray absorptiometry (DXA), mid-thigh MRI, and completed knee extensor and flexor torque assessments via isokinetic dynamometer. Manual segmentation of mid-thigh CSA was completed for all MRI scans. A convolutional neural network (CNN) was created based on the manual segmentation to develop automated quantification of mid-thigh CSA. Relationships were established between the automated CNN values to the manual CSA segmentation, ALM via DXA, knee extensor, and flexor torque. Results A total of 47 obese patients were enrolled in this study. Agreement between the CNN-automated measures and manual segmentation of mid-thigh CSA was high ( & gt;0.90). Automated measures of mid-thigh CSA were strongly related to the leg lean mass ( r = 0.86, p & lt; 0.001) and ALM ( r = 0.87, p & lt; 0.001). Additionally, mid-thigh CSA was strongly related to knee extensor strength ( r = 0.76, p & lt; 0.001) and moderately related to knee flexor strength ( r = 0.48, p = 0.002). Conclusion CNN-measured mid-thigh CSA was accurate compared to the manual segmented values from the mid-thigh. These values were strongly predictive of clinical measures of ALM and knee extensor torque. Mid-thigh MRI may be utilized to accurately estimate clinical measures of lean mass and function in obese adults.
    Type of Medium: Online Resource
    ISSN: 2673-6861
    URL: Article
    DOI: 10.3389/fresc.2022.808538
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 3091712-8
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  • 4
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    Maternal diet alters long-term innate immune cell memory in fetal and juvenile hematopoietic stem and progenitor cells in nonhuman primate offspring
    Elsevier BV ; 2023
    In:  Cell Reports Vol. 42, No. 4 ( 2023-04), p. 112393-
    Details
    In: Cell Reports, Elsevier BV, Vol. 42, No. 4 ( 2023-04), p. 112393-
    Type of Medium: Online Resource
    ISSN: 2211-1247
    URL: Article
    DOI: 10.1016/j.celrep.2023.112393
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2649101-1
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  • 5
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    Impaired fasting glucose with or without impaired glucose tolerance: progressive or parallel states of prediabetes?
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 295, No. 2 ( 2008-08), p. E428-E435
    Details
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 295, No. 2 ( 2008-08), p. E428-E435
    Abstract: Our objective was to determine whether defects underlying impaired fasting glucose (IFG) are maintained and additive when combined with impaired glucose tolerance (IGT) (representing a progressive form of prediabetes) or are distinct in IFG/IGT (reflecting a parallel form of prediabetes). Volunteers with IFG ( n = 10), IFG/IGT ( n = 14), or normal glucose tolerance (NGT; n = 15) were matched for demographics and anthropometry. Insulin secretion was assessed using the glucose step-up protocol and insulin action through the use of a two-stage hyperinsulinemic euglycemic clamp with infusion of [6,6- 2 H 2 ]glucose. Modeling of insulin secretory parameters revealed similar basal (Φ b ) but diminished dynamic (Φ d ) components in both IFG and IFG/IGT ( P = 0.05 vs. NGT for both). Basal glucose rate of appearance (R a ) was higher in IFG compared with NGT ( P 〈 0.01) and also, surprisingly, with IFG/IGT ( P 〈 0.04). Moreover, glucose R a suppressed more during the low-dose insulin clamp in IFG ( P 〈 0.01 vs. NGT, P = 0.08 vs. IFG/IGT). Insulin-stimulated glucose uptake [glucose rate of disappearance (R d )] was similar in IFG, IFG/IGT, and NGT throughout the clamp. We conclude that nuances of β-cell dysfunction observed in IFG were also noted in IFG/IGT. A trend for additional insulin secretory defects was observed in IFG/IGT, possibly suggesting progression in β-cell failure in this group. In contrast, basal glucose R a and its suppressability with insulin were higher in IFG, but not IFG/IGT, compared with NGT. Together, these data indicate that IFG/IGT may be a distinct prediabetic syndrome rather than progression from IFG.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    URL: Article
    DOI: 10.1152/ajpendo.90354.2008
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477331-4
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  • 6
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    Inflexibility in Intramuscular Triglyceride Fractional Synthesis Distinguishes Prediabetes From Obesity in Humans
    Wiley ; 2010
    In:  Obesity Vol. 18, No. 8 ( 2010-08), p. 1524-1531
    Details
    In: Obesity, Wiley, Vol. 18, No. 8 ( 2010-08), p. 1524-1531
    Type of Medium: Online Resource
    ISSN: 1930-7381
    URL: Article
    DOI: 10.1038/oby.2009.454
    Language: English
    Publisher: Wiley
    Publication Date: 2010
    detail.hit.zdb_id: 2027211-X
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  • 7
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    Intramuscular triglyceride synthesis: importance in muscle lipid partitioning in humans
    American Physiological Society ; 2018
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 314, No. 2 ( 2018-02-01), p. E152-E164
    Details
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 314, No. 2 ( 2018-02-01), p. E152-E164
    Abstract: Intramuscular triglyceride (IMTG) concentration is elevated in insulin-resistant individuals and was once thought to promote insulin resistance. However, endurance-trained athletes have equivalent concentration of IMTG compared with individuals with type 2 diabetes, and have very low risk of diabetes, termed the “athlete’s paradox.” We now know that IMTG synthesis is positively related to insulin sensitivity, but the exact mechanisms for this are unclear. To understand the relationship between IMTG synthesis and insulin sensitivity, we measured IMTG synthesis in obese control subjects, endurance-trained athletes, and individuals with type 2 diabetes during rest, exercise, and recovery. IMTG synthesis rates were positively related to insulin sensitivity, cytosolic accumulation of DAG, and decreased accumulation of C18:0 ceramide and glucosylceramide. Greater rates of IMTG synthesis in athletes were not explained by alterations in FFA concentration, DGAT1 mRNA expression, or protein content. IMTG synthesis during exercise in Ob and T2D indicate utilization as a fuel despite unchanged content, whereas IMTG concentration decreased during exercise in athletes. mRNA expression for genes involved in lipid desaturation and IMTG synthesis were increased after exercise and recovery. Further, in a subset of individuals, exercise decreased cytosolic and membrane di-saturated DAG content, which may help explain insulin sensitization after acute exercise. These data suggest IMTG synthesis rates may influence insulin sensitivity by altering intracellular lipid localization, and decreasing specific ceramide species that promote insulin resistance.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    URL: Article
    DOI: 10.1152/ajpendo.00142.2017
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2018
    detail.hit.zdb_id: 1477331-4
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  • 8
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    Intramuscular Lipid Metabolism in the Insulin Resistance of Smoking
    American Diabetes Association ; 2009
    In:  Diabetes Vol. 58, No. 10 ( 2009-10-01), p. 2220-2227
    Details
    In: Diabetes, American Diabetes Association, Vol. 58, No. 10 ( 2009-10-01), p. 2220-2227
    Abstract: Smoking decreases insulin action and increases the risk of type 2 diabetes in humans. Mechanisms responsible for smoking-induced insulin resistance are unclear. We hypothesized smokers would have increased intramuscular triglyceride (IMTG) and diacylglycerol (DAG) concentration and decreased fractional synthesis rate (FSR) compared with nonsmokers. RESEARCH DESIGN AND METHODS Nonsmokers (n = 18, aged 20 ± 0.5 years, BMI 22 ± 0.4 kg/m2, body fat 20 ± 2%, 0 cigarettes per day) and smokers (n = 14, aged 21 ± 0.7 years, BMI 23 ± 0.4 kg/m2, body fat 20 ± 3%, 18 ± 0.7 cigarettes per day) were studied in a fasted condition after a standardized diet. [U-13C]palmitate was infused during 4 h of rest followed by a skeletal muscle biopsy and intravenous glucose tolerance test. RESULTS Smokers were less insulin sensitive (Si) compared with nonsmokers (Si 5.28 ± 0.5 nonsmokers vs. 3.74 ± 0.3 smokers 10−4 · μU−1 · ml−1, P = 0.03). There were no differences in IMTG or DAG concentration (IMTG 24.2 ± 3.4 nonsmokers vs. 27.2 ± 5.9 smokers μg/mg dry wt, DAG 0.34 ± 0.02 nonsmokers vs. 0.35 ± 0.02 smokers μg/mg dry wt) or IMTG FSR between groups (0.66 ± 0.1 nonsmokers vs. 0.55 ± 0.09 smokers %/hr). Intramuscular lipid composition was different, with increased percent saturation of IMTG (32.1 ± 1.2 nonsmokers vs. 35.2 ± 1.0 smokers %, P = 0.05) and DAG (52.8 ± 1.7 nonsmokers vs. 58.8 ± 2.2 smokers %, P = 0.04) in smokers. Smokers had significantly decreased peroxisome proliferator–activated receptor-γ (1.76 ± 0.1 nonsmokers vs. 1.42 ± 0.11 smokers arbitrary units [AU] , P = 0.03) and increased monocyte chemotactic protein-1 (3.11 ± 0.41 nonsmokers vs. 4.83 ± 0.54 smokers AU, P = 0.02) mRNA expression compared with nonsmokers. We also found increased insulin receptor substrate-1 Ser636 phosphorylation in smokers compared with nonsmokers (0.73 ± 0.08 nonsmokers vs. 1.14 ± 0.09 smokers AU, P = 0.002). CONCLUSIONS These data suggest: 1) IMTG concentration and turnover are not related to alterations in insulin action in smokers compared to nonsmokers, 2) increased saturation of IMTG and DAG in skeletal muscle may be related to insulin action, and 3) basal inhibition of insulin receptor substrate-1 may decrease insulin action in smokers.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db09-0481
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2009
    detail.hit.zdb_id: 1501252-9
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  • 9
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    Pyruvate shuttling during rest and exercise before and after endurance training in men
    American Physiological Society ; 2004
    In:  Journal of Applied Physiology Vol. 97, No. 1 ( 2004-07), p. 317-325
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 97, No. 1 ( 2004-07), p. 317-325
    Abstract: We describe the isotopic exchange of lactate and pyruvate after arm vein infusion of [3- 13 C]lactate in men during rest and exercise. We tested the hypothesis that working muscle (limb net lactate and pyruvate exchange) is the source of the elevated systemic lactate-to-pyruvate concentration ratio (L/P) during exercise. We also hypothesized that the isotopic equilibration between lactate and pyruvate would decrease in arterial blood as glycolytic flux, as determined by relative exercise intensity, increased. Nine men were studied at rest and during exercise before and after 9 wk of endurance training. Although during exercise arterial pyruvate concentration decreased to below rest values ( P 〈 0.05), pyruvate net release from working muscle was as large as lactate net release under all exercise conditions. Exogenous (arterial) lactate was the predominant origin of pyruvate released from working muscle. With no significant effect of exercise intensity or training, arterial isotopic equilibration [(IE pyruvate /IE lactate )·100%, where IE is isotopic enrichment] decreased significantly ( P 〈 0.05) from 60 ± 3.1% at rest to an average value of 12 ± 2.7% during exercise, and there were no changes in femoral venous isotopic equilibration. These data show that 1) the isotopic equilibration between lactate and pyruvate in arterial blood decreases significantly during exercise; 2) working muscle is not solely responsible for the decreased arterial isotopic equilibration or elevated arterial L/P occurring during exercise; 3) working muscle releases similar amounts of lactate and pyruvate, the predominant source of the latter being arterial lactate; 4) pyruvate clearance from blood occurs extensively outside of working muscle; and 5) working muscle also releases alanine, but alanine release is an order of magnitude smaller than lactate or pyruvate release. These results portray the complexity of metabolic integration among diverse tissue beds in vivo.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.01367.2003
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2004
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 10
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    Increased intramuscular lipid synthesis and low saturation relate to insulin sensitivity in endurance-trained athletes
    American Physiological Society ; 2010
    In:  Journal of Applied Physiology Vol. 108, No. 5 ( 2010-05), p. 1134-1141
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 108, No. 5 ( 2010-05), p. 1134-1141
    Abstract: Intramuscular triglyceride (IMTG) has received considerable attention as a potential mechanism promoting insulin resistance. Endurance-trained athletes have high amounts of IMTG but are insulin sensitive, suggesting IMTG content alone does not change insulin action. Recent data suggest increased muscle lipid synthesis protects against fat-induced insulin resistance. We hypothesized that rates of IMTG synthesis at rest would be increased in athletes compared with controls. Eleven sedentary men and 11 endurance-trained male cyclists participated in this study. An intravenous glucose tolerance test was performed to assess insulin action. After 3 days of dietary control and an overnight fast, [ 13 C 16 ]palmitate was infused at 0.0174 μmol·kg −1 ·min −1 for 4 h, followed by a muscle biopsy to measure isotope incorporation into IMTG and diacylglycerol. Compared with controls, athletes were twice as insulin sensitive ( P = 0.004) and had a significantly greater resting IMTG concentration (athletes: 20.4 ± 1.6 μg IMTG/mg dry wt, controls: 14.5 ± 1.8 μg IMTG/mg dry wt, P = 0.04) and IMTG fractional synthesis rate (athletes: 1.56 ± 0.37%/h, controls: 0.61 ± 0.15%/h, P = 0.03). Stearoyl-CoA desaturase 1 mRNA expression ( P = 0.02) and protein content ( P = 0.03) were also significantly greater in athletes. Diacylglycerol, but not IMTG, saturation was significantly less in athletes compared with controls ( P = 0.002). These data indicate endurance-trained athletes have increased synthesis rates of skeletal muscle IMTG and decreased saturation of skeletal muscle diacylglycerol. Increased synthesis rates are not due to recovery from exercise and are likely adaptations to chronic endurance exercise training.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.00684.2009
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2010
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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