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  • 1
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 292, No. 1 ( 2007-01), p. E40-E48
    Abstract: HIV infection is associated with abnormal lipid metabolism, body fat redistribution, and altered energy expenditure. The pathogenesis of these complex abnormalities is unclear. Viral protein R (Vpr), an HIV-1 accessory protein, can regulate gene transcription mediated by the glucocorticoid receptor and peroxisome proliferator-activated receptor-γ and affect mitochondrial function in vitro. To test the hypothesis that expression of Vpr in liver and adipocytes can alter lipid metabolism in vivo, we engineered mice to express Vpr under control of the phospho enolpyruvate carboxykinase promoter in a tissue-specific and inducible manner and investigated the effects of dietary fat, indinavir, and dexamethasone on energy metabolism and body composition. The transgenic mice expressed Vpr mRNA in white and brown adipose tissues and liver and immunoaffinity capillary electrophoresis revealed that they had free Vpr protein in the plasma. Compared with wild-type (WT) animals, Vpr mice had lower plasma triglyceride levels after 6 wk ( P 〈 0.05) but not after 10 wk of a high-fat diet and lower plasma cholesterol levels after 10 wk of high-fat diet ( P 〈 0.05). Treatment with dexamethasone obviated group differences, whereas indinavir had no significant independent effect on lipids. In the fasted state, Vpr mice had a higher respiratory quotient than WT mice ( P 〈 0.05). These data provide the first in vivo evidence that HIV-1 Vpr expressed at low levels in adipose tissues and liver can 1) circulate in the blood, 2) regulate lipid and fatty acid metabolism, and 3) alter fuel selection for oxidation in the fasted state.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1477331-4
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  • 2
    Online Resource
    Online Resource
    American Physiological Society ; 1999
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 277, No. 5 ( 1999-11-01), p. E905-E914
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 277, No. 5 ( 1999-11-01), p. E905-E914
    Abstract: We investigated the effect of nutrient intake on glucose metabolism in normal Mexican-Americans ( n = 6) and European-Americans ( n = 6). Subjects were studied after an 18-h fast and after 5–6 h of ingestion of hourly meals that supplied 6.35 or 12.75 μmol glucose ⋅ kg −1 ⋅ min −1 . Endogenous glucose production (EGP), gluconeogenesis (GNG), and glycogenolysis (GLY) were estimated by mass isotopomer analysis with [U- 13 C]glucose infusions. Fasting EGP, GNG, and GLY did not differ between the groups. Food ingestion lowered the molar rate of GNG by only 31%. However, while consuming the lower quantity of nutrients, Mexican-Americans had higher plasma glucose ( P 〈 0.05), a 39% higher rate of EGP ( P 〈 0.05), and a 68% ( P 〈 0.025) higher rate of GLY than the European-Americans. At the higher intake, EGP and GLY were suppressed completely in both groups. There was a linear relationship between insulin concentrations, EGP, and GLY in both groups, but the slope of the line was significantly ( P 〈 0.05) greater in the European-Americans. We conclude that the sensitivity of GLY to nutrient intake differs between ethnic groups and that this may play a role in the increased predisposition of Mexican-Americans to type II diabetes.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    Language: English
    Publisher: American Physiological Society
    Publication Date: 1999
    detail.hit.zdb_id: 1477331-4
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    American Physiological Society ; 2014
    In:  Journal of Applied Physiology Vol. 117, No. 4 ( 2014-08-15), p. 377-382
    In: Journal of Applied Physiology, American Physiological Society, Vol. 117, No. 4 ( 2014-08-15), p. 377-382
    Abstract: Whether lean body mass (LBM) composition, especially skeletal muscle and abdominal organs, differs in adults with type 2 diabetes (T2DM) compared with nondiabetic healthy controls has not been investigated. A subset of African-American and Caucasian participants with T2DM from the Look AHEAD (Action for Health in Diabetes) trial had body composition assessed and compared with a sample of healthy controls. Skeletal muscle mass (SMM), liver, kidneys, and spleen mass were quantified using a contiguous slice magnetic resonance imaging (MRI) protocol. Cardiac mass was quantified by either a cardiac gated MRI protocol or by echocardiography. MRI volumes were converted to mass using assumed densities. Dual-energy X-ray absorptiometry assessed LBM. Using general linear models adjusted for height, weight, sex, age, race, and interactions of diabetes status with race or sex, persons with T2DM ( n = 95) had less LBM (49.7 vs. 51.6 kg) and SMM (24.1 vs. 25.4 kg) and larger kidneys (0.40 vs. 0.36 kg) than controls ( n = 76) (all P 〈 0.01). Caucasians with T2DM had larger livers (1.90 vs. 1.60 kg, P 〈 0.0001) and spleens (0.29 vs. 0.22 kg, P 〈 0.01), and T2DM men had less cardiac mass than controls (0.25 vs. 0.30 kg, P 〈 0.001). In this sample, T2DM is characterized by less relative skeletal muscle and cardiac mass in conjunction with larger kidneys, liver, and spleen. Further investigation is needed to establish the causes and metabolic consequences of these race- and sex-specific organ mass differences in T2DM.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    RVK:
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2014
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 4
    Online Resource
    Online Resource
    American Physiological Society ; 2002
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 283, No. 2 ( 2002-08-01), p. E332-E337
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 283, No. 2 ( 2002-08-01), p. E332-E337
    Abstract: Human immunodeficiency virus (HIV)-lipodystrophy syndrome (HLS) is characterized by hypertriglyceridemia, low high-density lipoprotein-cholesterol, lipoatrophy, and central adiposity. We investigated fasting lipid metabolism in six men with HLS and six non-HIV-infected controls. Compared with controls, HLS patients had lower fat mass (15.9 ± 1.3 vs. 22.3 ± 1.7 kg, P 〈 0.05) but higher plasma glycerol rate of appearance (R a ), an index of total lipolysis (964.71 ± 103.33 vs. 611.08 ± 63.38 μmol · kg fat −1 · h −1 , P 〈 0.05), R a palmitate, an index of net lipolysis (731.49 ± 72.36 vs. 419.72 ± 33.78 μmol · kg fat −1 · h −1 , P 〈 0.01), R a free fatty acids (2,094.74 ± 182.18 vs. 1,470.87 ± 202.80 μmol · kg fat −1 · h −1 , P 〈 0.05), and rates of intra-adipocyte (799.40 ± 157.69 vs. 362.36 ± 74.87 μmol · kg fat −1 · h −1 , P 〈 0.01) and intrahepatic fatty acid reesterification (1,352.08 ± 123.90 vs. 955.56 ± 124.09 μmol · kg fat −1 · h −1 , P 〈 0.05). Resting energy expenditure was increased in HLS patients (30.51 ± 2.53 vs. 25.34 ± 1.04 kcal · kg lean body mass −1 · day −1 , P 〈 0.05), associated with increased non-plasma-derived fatty acid oxidation (139.04 ± 24.17 vs. 47.87 ± 18.81 μmol · kg lean body mass −1 · min −1 , P 〈 0.02). The lipoatrophy observed in HIV lipodystrophy is associated with accelerated lipolysis. Increased hepatic reesterification promotes the hypertriglyceridemia observed in this syndrome.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2002
    detail.hit.zdb_id: 1477331-4
    SSG: 12
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  • 5
    In: Physiological Genomics, American Physiological Society, Vol. 47, No. 6 ( 2015-06), p. 215-224
    Abstract: Overweight/obese individuals with Type 2 diabetes have low adiponectin levels, which may improve with lifestyle changes. We investigated whether genetic variants associated with adiponectin levels in genome-wide association studies (GWAS) would also be related with adiponectin changes in response to an intensive lifestyle intervention (ILI), potentially through mechanisms altering the adipose microenvironment via weight loss and/or improved cardiorespiratory fitness. Look AHEAD was a randomized trial comparing the cardiovascular benefits of ILI-induced weight loss and physical activity compared with diabetes support and education among overweight/obese individuals with Type 2 diabetes. In a subsample of Look AHEAD with adiponectin data and genetic consent ( n = 1,351), we evaluated the effects of 24 genetic variants, demonstrated by GWAS to be cross-sectionally associated with adiponectin, on adiponectin change 1-yr postintervention. We explored via mediational analyses whether any differential effects by treatment arm were occurring through weight loss and/or improved fitness. A variant, rs222857, in the CLDN7 locus, potentially associated with epithelial barrier integrity and tight junction physiology, and a putative cis expression quantitative trail locus for elongator acetyltransferase complex subunit 5 ( ELP5), predicted adiponectin increases within ILI (log-adiponectin in overall sample per copy: β ± SE = 0.05 ± 0.02, P = 0.008; in non-Hispanic whites: 0.06 ± 0.02, P = 0.009). The favorable effects of rs222857 (minor allele frequency 45.5%) appeared to be mediated by mechanisms associated with improved fitness, and not weight loss. This is the first study to identify a genetic variant that modifies adiponectin response to lifestyle intervention in overweight/obese diabetic individuals.
    Type of Medium: Online Resource
    ISSN: 1094-8341 , 1531-2267
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2015
    detail.hit.zdb_id: 2031330-5
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