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Publications (44)
Alcohol use disorders (AUDs) frequently exist among persons living with HIV/AIDS (PLWHA). Chronic alcohol consumption, HIV infection, and anti-retroviral therapy (ART) are independently associated with impairments in glucose-insulin dynamics. Previous studies from our laboratory have shown that chronic binge alcohol (CBA) administration decreases b...
Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), the primary psychoactive component in marijuana, is FDA approved to ameliorate AIDS-associated wasting. Because cannabinoid receptors are expressed on cells of the immune system, chronic Δ(9)-THC use may impact HIV disease progression. We examined the impact of chronic Δ(9)-THC administration (0.32 mg/kg im, 2...
Increasing numbers of Americans are reaching 85 years of age or older, yet there are no reliable biomarkers to predict who will live this long. The goal of this pilot study therefore was: (1) to identify a potential serum pattern that could identify proteins involved in longevity and (2) to determine if this pattern was a marker of longevity in an...
Atypical antipsychotic medications like olanzapine (OLZ) induce weight gain and increase the risk of diabetes in patients with schizophrenia. The goal of this study was to assess potential mechanisms of OLZ-induced weight gain and accompanying metabolic effects. Healthy, lean, male volunteers received OLZ and placebo (PBO) in a randomized, double-b...
We provide evidence that a factor other than the previously identified lipid mobilizing factor, zinc alpha-2 glycoprotein, promotes lipolysis in the MCA-induced sarcoma-bearing cachexia model. Cachexia is characterized by progressive loss of adipose tissue and skeletal muscle without a concurrent increase in food intake to restore lost tissue store...
Research into the age-associated decline in the immune system has focused on the factors that contribute to the accumulation of senescent CD8 T cells. Less attention has been paid to the non-immune factors that may maintain the pool of naïve CD8 T cells. Here, we analyzed the status of the naïve CD8 T-cell population in healthy nonagenarians (≥90-y...
A sudden increase in exercise and energy expenditure is associated with an increase in protein turnover and nitrogen excretion. This study examined how a sudden increase in exercise-induced energy expenditure affected whole body protein metabolism and nitrogen balance in people of differing levels of aerobic fitness. We hypothesized that alteration...
This study assessed cardiovascular disease risk factors in three groups of human subjects aged 20–34 [young, 20 male (M)/33 female (F)], 60–74 (aged, 29M/29F), and > 90 years (nonagenarian, 47M/50F). Components of the metabolic syndrome, cardiovascular disease, and markers of inflammation and oxidative stress were assessed. Nonagenarians weighed le...
This study examined how a high-protein diet affected nitrogen balance and protein turnover during an exercise-induced energy deficit.
Twenty-two men completed a 4-d (D1-4) baseline period (BL) of an energy balance diet while maintaining usual physical activity level, followed by 7 d (D5-11) of 1000 kcal.d increased energy expenditure via exercise (...
We demonstrated previously that food intake traits map to a quantitative trait locus (QTL) on proximal chromosome 17, which encompasses Glp1r (glucagon-like peptide 1 receptor), encoding an important modulator of gastric emptying. We then confirmed this QTL in a B6.CAST-17 congenic strain that consumed 27% more carbohydrate and 17% more total calor...
We have recently reported that, during moderate intensity exercise, low muscle glycogen concentration and utilization caused by a high-fat diet is associated with a marked increase in fat oxidation with no effect on plasma glucose uptake (R(d) glucose). It is our hypothesis that this increase in fat oxidation compensates for low muscle glycogen, th...
This study determined the role of intramuscular triglyceride (IMTG) and adipose lipolysis in the elevated fat oxidation during exercise caused by a high-fat diet. In four separate trials, six endurance-trained cyclists exercised at 50% peak O2 consumption for 1 h after a two-day control diet (22% fat, CON) or an isocaloric high-fat diet (60% fat, H...
The minimal model of glucose disappearance (MINMOD version 3; MM3) and both the one-compartment (1CMM) and the two-compartment (2CMM) minimal models were used to analyze stable isotope-labeled intravenous glucose tolerance test (IVGTT) data from year 10 of a study of the effect of dietary restriction (DR) in male rhesus monkeys. Adult monkeys were...
The glycemic index (GI) of a food is thought to directly reflect the rate of digestion and entry of glucose into the systemic circulation. The blood glucose concentration, however, represents a balance of both the entry and the removal of glucose into and from the blood, respectively. Such direct quantification of the postprandial glucose curve wit...
The mechanism for cellular Zn uptake was investigated by depleting cell cholesterol levels, a treatment that disrupts lipid rafts/caveolae-dependent processes and inhibits coated-pit budding. Incubation of MCF-10A human breast epithelial cells with hydroxypropyl-beta-cyclodextrin significantly lowered cell cholesterol levels and significantly inhib...
We used beta-adrenergic receptor stimulation and blockade as a tool to study substrate metabolism during exercise. Eight moderately trained subjects cycled for 60 min at 45% of VO(2 peak) 1) during a control trial (CON); 2) while epinephrine was intravenously infused at 0.015 microg. kg(-1) x min(-1) (beta-STIM); 3) after ingesting 80 mg of propran...
This investigation determined whether ingestion of a tolerable amount of medium-chain triglycerides (MCT; approximately 25 g) reduces the rate of muscle glycogen use during high-intensity exercise. On two occasions, seven well-trained men cycled for 30 min at 84% maximal O(2) uptake. Exactly 1 h before exercise, they ingested either 1) carbohydrate...
This study determined the effect of carbohydrate ingestion during exercise on the lipolytic rate, glucose disappearance from plasma (Rd Glc), and fat oxidation. Six moderately trained men cycled for 2 h on four separate occasions. During two trials, they were fed a high-glycemic carbohydrate meal during exercise at 30 min (0.8 g/kg), 60 min (0.4 g/...
This study determined if the suppression of lipolysis after preexercise carbohydrate ingestion reduces fat oxidation during exercise. Six healthy, active men cycled 60 min at 44 +/- 2% peak oxygen consumption, exactly 1 h after ingesting 0.8 g/kg of glucose (Glc) or fructose (Fru) or after an overnight fast (Fast). The mean plasma insulin concentra...
This study determined if the suppression of lipolysis after preexercise carbohydrate ingestion reduces fat oxidation during exercise. Six healthy, active men cycled 60 min at 44 ± 2% peak oxygen consumption, exactly 1 h after ingesting 0.8 g/kg of glucose (Glc) or fructose (Fru) or after an overnight fast (Fast). The mean plasma insulin concentrati...
This study was designed to allow carbohydrate ingestion to increase glucose disappearance from plasma (Rd glucose) with minimal suppression of lipolysis, to determine the effect of an increase in glucose uptake by muscle on fat oxidation during exercise. On two occasions, six moderately trained men cycled for 2h at low intensity (25% VO2peak): once...
The adaptation to fasting reduces muscle protein breakdown by switching from a carbohydrate to fat fuel economy in normal man. With the discovery of T3 and the observation that its formation from T4 was reduced significantly during starvation, it was proposed that T3 mediated many of these changes. To examine this possibility, otherwise healthy, ob...
The adaptation to fasting reduces muscle protein breakdown by switching from a carbohydrate to fat fuel economy in normal man. With the discovery of T3 and the observation that its formation from T4 was reduced significantly during starvation, it was proposed that T3 mediated many of these changes. To examine this possibility, otherwise healthy, ob...
In order to determine whether protein (PRO) has specific benefits on protein breakdown in obese patients not provided by carbohydrate (CHO) as part of a VLCD, 30 healthy obese subjects were studied under metabolic ward conditions using ketones, thyroid hormones, estimated nitrogen balance (N bal) and primed constant infusions of 6-3H glucose (gluco...
A high fat diet fed ad libitum will promote breast tumorigenesis in rats while caloric restriction of the same high fat diet counteracts this promotional effect. The present study examined the effects of dietary fat and calorie intake on adipose tissue weight and fatty acid composition and on tumor incidence and development. The sites of adipose ti...
To determine the contributions of preexisting fatty acid, de novo synthesis, and chain elongation in long-chain fatty acid (LCFA) synthesis, the synthesis of LCFAs, palmitate (16:0), stearate (18:0), arachidate (20:0), behenate (22:0), and lignocerate (24:0), in the epidermis, liver, and spinal cord was determined using deuterated water and mass is...
Recent developments in the application of stable isotopes and mass spectrometry have permitted the estimation of precursor enrichment and fractional synthesis of the product through mass isotopomer analysis. Thus, the application of isotopomer analysis in studies with 2H- and 13C-labeled glucose may potentially overcome the limitations of tradition...
The synthesis of palmitate, stearate, and cholesterol in liver and nervous tissues (brain, cord, and nerve) of Sprague-Dawley rats was determined using deuterated water (D2O) and mass isotopomer analysis. Rats were given 4% deuterium in their drinking water after each receiving an intraperitoneal priming dose. Animals were killed at 1, 2, 4, and 8...
Fractional biosynthesis of palmitate, stearate, and cholesterol was determined with deuterated water (2H2O) using mass isotopomer analysis in Hep G2 and MCA sarcoma cells in culture. The method employed differs from previous ones in that the number of deuterium atoms from 2H2O incorporated into newly synthesized molecules was determined and not ass...
Many common metastatic cancers are associated with marked weight loss at the time of diagnosis. Anorexia clearly plays a major role in weight loss in the cancer patient, but cannot explain all of the weight loss noted. Malnourished patients with localized cancers under metabolic ward conditions fail to gain weight when given apparently adequate cal...
The relationships between metabolic alterations and tissue-specific gene expression of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), gamma-interferon (gamma-IFN), and interleukin 1 and serum levels of TNF-alpha and IL-6 before and after a live Escherichia coli septic challenge to rats were examined. From 0 to 2 h, serum glucose sig...
A theory of mass isotopomer analysis based on the well-known principle of isotope dilution mass spectrometry is reviewed. An algorithm for the determination of isotope incorporation into a metabolic substrate from a labeled precursor using mass isotopomer analysis is presented. The steps include the determination of the contribution of the derivati...
Cachexia is a phenomenon commonly observed in patients with cancer, but its etiology is poorly understood. Abnormalities of insulin action and metabolism that have been hypothesized to promote cancer cachexia were investigated in this study using a computerized euglycemic clamp and modified frequently sampled intravenous glucose tolerance test (FSI...
Cancer commonly leads to weight loss associated with increased glucose production and protein breakdown. Medical or surgical castration results in decreased muscle mass, increased fat mass, and weight gain. The aim of this study was to evaluate the changes in body composition, protein metabolism, hepatic glucose production, (HGP), and basal energy...
A large body of epidemiologic evidence and data drawn from animal feeding studies have led to the feasibility testing of clinical breast cancer prevention trials based on the restriction of dietary fat intake. The animal data strongly suggest that restricting calories as well as fat inhibits breast cancer promotion. Body fat correlates with dietary...
A number of common metastatic cancers are associated with marked weight loss at the time of diagnosis. Cancer patients with weight loss at the time of diagnosis have decreased mean survival compared to similar cancer patients without weight loss. Provision of excess calories alone does not appear to change median survival in patients with advanced...
A number of common metastatic cancers are associated with marked weight loss at the time of diagnosis. Cancer patients with weight loss at the time of diagnosis have decreased mean survival compared to similar cancer patients without weight loss. Provision of excess calories alone does not appear to change median survival in patients with advanced...