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Biomedical subjects

J S Stern

Publications and source records attributed to J S Stern.

At least 55 records · Page 3Linked to original sources
PubMed1998

Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes.

Circulating leptin secreted from adipocytes is correlated with fat mass and plasma insulin concentrations in humans and rodents. Plasma leptin, insulin, and glucose decrease during fasting and increase after refeeding; however, the underlying mechanisms regulating the changes of leptin secretion are not known. To investigate the role of insulin-stimulated glucose metabolism in the regulation of leptin secretion, we examined the effects of insulin and inhibitors of glucose transport and metabolism on leptin secretion from rat adipocytes in primary culture. Insulin (0.16-16 nM) increased leptin secretion over 96 h; however, the increase in leptin was more closely related to the amount of glucose taken up by the adipocytes (r = 0.64; P < 0.0001) than to the insulin concentration per se (r = 0.20; P < 0.28), suggesting a role for glucose transport and/or metabolism in regulating leptin secretion. 2-Deoxy-D-glucose (2-DG), a competitive inhibitor of glucose transport and phosphorylation, caused a concentration-dependent (2-50 mg/dl) inhibition of leptin release in the presence of 1.6 nM insulin. The inhibitory effect of 2-DG was reversed by high concentrations of glucose. Two other inhibitors of glucose transport, phloretin (0.05-0.25 mM) and cytochalasin-B (0.5-50 microM), also inhibited leptin secretion. Inhibition of leptin secretion by these agents was proportional to the inhibition of glucose uptake (r = 0.60 to 0.86; all P < 0.01). Two inhibitors of glycolysis, iodoacetate (0.005-1.0 mM) and sodium fluoride (0.1-5 mM), produced concentration-dependent inhibition of leptin secretion in the presence of 1.6 nM insulin. In addition, both 2-DG and sodium fluoride markedly decreased the leptin (ob) messenger RNA content of cultured adipocytes, but did not affect 18S ribosomal RNA content. We conclude that glucose transport and metabolism are important factors in the regulation of leptin expression and secretion and that the effect of insulin to increase adipocyte glucose utilization is likely to contribute to insulin-stimulated leptin secretion. Thus, in vivo, decreased adipose glucose metabolism may be one mechanism by which fasting decreases circulating leptin, whereas increased adipose glucose metabolism would increase leptin after refeeding.

Adipocytes↗
PubMed1997

Nutritional management of cardiovascular risk factors. A randomized clinical trial.

BACKGROUND: Adherence to dietary recommendations for disease management is often hindered by the complexity of incorporating them into the daily diet. Nutrition and cardiovascular scientists and food technologists collaborated to develop a prepared meal plan that meets national dietary guidelines for cardiovascular risk reduction. OBJECTIVE: To assess the clinical effects of this plan, which incorporates all National Academy of Sciences National Research Council recommended dietary allowances for vitamins, minerals, and macronutrients, compared with a patient-selected American Heart Association Step I and Step II diet plan. METHODS: This multicenter, randomized, parallel-intervention trial was conducted at 10 medical centers in the United States and Canada and involved 560 men and women with hypertension, dyslipidemia, or diabetes. Following calculation of prescriptions to meet individual nutritional requirements based on the Harris-Benedict equation, participants were randomized to the Campbell's Center for Nutrition and Wellness (CCNW) plan, which is composed of prepackaged breakfast, lunch, and dinner meals provided to participants, or a nutritionist-guided American Heart Association Step I and Step II diet, in which participants self-selected foods to meet their nutrition prescription for 10 weeks. MAIN OUTCOME MEASURES: Blood pressure (BP); lipid, glucose, glycosylated hemoglobin (HbA1c), and insulin levels; body weight; dietary intake; and quality of life. RESULTS: Patients' BP, lipid levels, carbohydrate metabolism, weight, and quality of life (P < or = .001 for all findings except low-density lipoprotein-high-density lipoprotein ratio, P = .25) all improved on both nutrition plans. Mean differences (+/-SD) between baseline and treatment clinical values for the CCNW and the self-selected diet groups (between-group P values), respectively, were as follows: systolic BP, -6.4 +/- 9.2 mm Hg and -4.6 +/- 9.0 mm Hg (P = .02); diastolic BP, -4.2 +/- 5.7 mm Hg and -3.0 +/- 5.1 mm Hg (P = .006); cholesterol, -0.32 +/- 0.58 mmol/L and -0.27 +/- 0.56 mmol/L (-12.4 +/- 22.5 mg/dL and -10.4 +/- 21.9 mg/dL) (P = .30); glucose, -0.65 +/- 1.88 mmol/L and -0.75 +/- 2.03 mmol/L (-11.7 +/- 34.0 mg/dL and -13.5 +/- 36.6 mg/dL) (P = .10); and HbA1c, -0.4% +/- 0.8% and -0.3% +/- 0.7% (P = .66). Weight loss with the CCNW and self-selected plans, respectively, was as follows: men, -4.5 +/- 3.6 kg and -3.5 +/- 3.3 kg; and women, -4.8 +/- 3.0 kg and -2.8 +/- 2.8 kg. Quality of life was significantly improved for daily and work activities (P < .05) and nutritional health perceptions (P < .05) with the CCNW plan relative to the self-selected group. Overall nutrient intake and compliance were both significantly (P < .001) better with the CCNW plan. CONCLUSIONS: Nutritionally balanced meals that meet the recommendations of national health organizations improved multiple risk factors for patients with cardiovascular disease. The CCNW plan resulted in greater clinical benefits, nutritional completeness, and compliance than the self-selected diet. The CCNW is a comprehensive nutrition plan, convenient for both prescription and practice, and appears viable for effecting favorable dietary changes in patients at high risk for cardiovascular disease.

Adult↗
PubMed1997

Changes of islet size and islet size distribution resulting from protein-malnutrition in lean (Fa/Fa) and obese (fa/fa) Zucker rats.

Potential alterations in islet size and islet size distribution resulting from protein malnutrition were studied in lean (Fa/Fa) and obese (fa/fa) Zucker rats. The purpose was to investigate whether the distribution of enlarged islets in obese rats was altered by low-protein feeding. Four-week-old, male, lean and obese Zucker rats were fed either a diet containing 20% (w/w) protein (control diet) or a diet containing 5% (w/w) protein (low-protein diet) for 3 weeks. Pancreata were dissected at autopsy and immunostained for insulin. Islet size and distribution were determined by morphometric analysis. Bodyweight gain, food intake, and serum insulin and glucose were also measured. After 3 weeks on the diets, serum insulin was significantly lower in both lean (-75%) and obese (-54%) rats fed low protein compared with that in controls. However, obese rats were still hyperinsulinemic compared with lean rats. Protein malnutrition resulted in a shift in distribution of islets to smaller size both in lean and in obese rats, with an increase in the population of small islets (< or = 100 microns2) and a decrease in the population of large islets (> 20,000 microns2). In lean and obese rats fed low protein, beta-cell weight was significantly lower, beta cell volume fraction tended to decrease, and islet number per section area was significantly elevated when compared with controls. Taken together, these results show that protein deficiency alters the endocrine pancrease in both lean and obese Zucker rats. Although the decrease in islet size and the shift in distribution to smaller islets most likely contribute to the decrease in serum insulin concentration, these changes appear insufficient to normalize hyperinsulinemia in the obese Zucker rat.

Animals↗
PubMed1997

Tics associated with autistic and pervasive developmental disorders.

Coincident cases of Tourette syndrome and Pervasive Developmental Disorders increasingly have been reported in the literature. Coincident cases currently number around 90. A minority of cases have been associated with cases of Tourette syndrome and tics in other family members; this has led some authors to suggest that Tourette syndrome may be responsible for some of the genetic heterogeneity in Pervasive Developmental Disorders. The literature is reviewed, along with some aspects of the neurobiology of the two conditions with arguments for and against this hypothesis.

Autistic Disorder↗
PubMed1997

Dietary compliance and cardiovascular risk reduction with a prepared meal plan compared with a self-selected diet.

Noncompliance with therapeutic diets remains a major obstacle to achieving improvements in cardiovascular disease (CVD) morbidity and mortality. This study compared dietary compliance and CVD risk factor response to two dietary interventions designed to treat hypertension, dyslipidemia, and diabetes mellitus. In a multicenter trial, 560 adults were randomly assigned to either a self-selected, mixed-food plan (n = 277), or a nutrient-fortified prepared meal plan (n = 283); each was designed to provide 15-20% of energy from fat, 55-60% from carbohydrate, and 15-20% from protein. Nutrient intake was estimated from 3-d food records collected biweekly throughout the 10-wk intervention. Compliance was determined by evaluating the participants' ability to meet specific criteria for energy intake [+/-420 kJ (100 kcal) from the midpoint of the prescribed energy range], fat intake (< 20%, < 25%, or < 30% of energy from total fat), and the National Cholesterol Education Program/American Heart Association Step 1 and 2 diet recommendations. Compliance with energy, fat, and Step 1 and 2 criteria was better in participants who followed the prepared meal plan than in those who followed the self-selected diet (P < 0.0001). Compliant participants in both groups achieved greater reductions in body weight, systolic and diastolic blood pressure, and total and low-density-lipoprotein cholesterol than noncompliant participants (P < 0.05). In general, better endpoint responses were observed with lower fat intakes regardless of group assignment. The prepared meal plan is a simple and effective strategy for meeting the many nutrient recommendations for CVD risk reduction and improving dietary compliance and CVD endpoints.

Adult↗
PubMed1997

Longevity in obese and lean male and female rats of the Zucker strain: prevention of hyperphagia.

Zucker obese (fa/fa) and lean (Fa/Fa) rats were fed a soy protein diet ad libitum under barrier conditions from 4 wk of age until death. Obese rats were also pair fed with lean controls to prevent hyperphagia. Time of death was determined and tissues collected at necropsy for histologic examination. Lean rats had longer 10th percentile survivorship (males 966 compared with 667 d, females 983 compared with 620 d) and maximum life spans (males 1067 compared with 803 d, females 1163 compared with 744 d) than did obese rats. Preventing hyperphagia increased maximum life span in both males (1010 d) and females (975 d). Pathologies in lean rats were similar to those reported for other rodent strains. For obese rats fed ad libitum, end-stage renal disease (ESRD) was the major cause of mortality (males: 91.1%, females: 93.3%). Prevention of hyperphagia decreased deaths attributable to ESRD (males: 64.4%, females: 51.1%). A smaller restriction in energy intake (8-18%) required to prevent hyperphagia compared with the 35-40% in most other studies produced similar increases in longevity, suggesting that obese Zucker rats are particularly sensitive to energy restriction. Amelioration of early onset of renal disease is a likely explanation. Percentage body fat in food-restricted obese rats did not differ from that of animals fed ad libitum; thus, reduced longevity is not the result of obesity per se, but rather is influenced by other metabolic pathologies occurring in this strain of rats homozygous for the fa gene. Because microalbuminuria with progression to ESRD is a complication in human obesity, the Zucker strain offers the opportunity to investigate initiating mechanisms of this pathology.

Aging↗
PubMed1997

Complementary medicine: a review of immunomodulatory effects of Chinese herbal medicines.

Popular demand for and scientific interest in complementary or alternative medicine, particularly medicinal botanicals, has increased considerably in recent years. The medicinal botanicals with the longest tradition, and for which extensive data are available, are Chinese herbal medicines and their Japanese counterparts--Kampo medicines. This review focuses on some representative examples of studies examining the effects of some traditional Chinese medicines on various aspects of the immune response. In vitro as well as in vivo studies are cited, the latter including not only animal experiments but also clinical trials. Although by no means exhaustive, this review attempts to show that much research has focused on the specific beneficial effects of Chinese herbal medicines. Studies examining the mechanisms by which they exert their immunomodulatory actions, however, are found much less frequently. Nonetheless, even the limited number of mechanistic experiments presented here reveal that numerous mechanisms are likely involved in the various actions of even a single medicine. It will be the elucidation of such mechanisms that will provide the scientific basis for establishing the efficacy and safety of not only Chinese herbal medicines but all forms of medicinal botanicals.

Animals↗
PubMed1997

The Gilles de la Tourette syndrome.

The Gilles de la Tourette syndrome is a neuropsychiatric condition characterized by waxing and waning tics, both vocal and motor, over a lifelong course with an onset under the age of 21 years. Once considered a rare curiosity, its prevalence is now agreed to be around 5/10,000, and is seen worldwide. Many cases are mild and never require medical attention. It is now thought to have a genetic basis, but linkage has not yet been achieved, owing possibly to the inadequacy of a single-gene hypothesis. There is a strong association with obsessive compulsive disorder, and some postulate that many other psychiatric conditions may be determined as variations of the same phenotype. Attention deficit hyperactivity disorder is also common among sufferers. Management is with a combination of psychosocial measures and drugs; in particular dopamine antagonists, the efficacy of which has led to the theory that the syndrome is caused by an abnormality of the dopaminergic system. Studies using functional imaging techniques have both supported and rejected this hypothesis. Future research is expected to concentrate on the further application of genetic and brain imaging techniques in addition to clinical trials to identify optimal treatments. Studies relating to clinical, genetic, etiological, and historical aspects are reviewed.

Brain↗
PubMed1996

Copper absorption, endogenous excretion, and distribution in Sprague-Dawley and lean (Fa/Fa) Zucker rats.

We previously observed a rapid reduction in plasma ceruloplasmin activity in lean Zucker (Fa/Fa) rats fed a marginal copper (Cu)-deficient diet compared to similarly fed obese Zucker (fa/fa) and lean Sprague-Dawley rats. In an effort to understand the mechanisms underlying this response, we utilized the isotope dilution method to investigate the absorption and excretion of Cu in lean Zucker rats fed control and marginal Cu diet. Sprague-Dawley (SD) and homozygous lean Zucker rats were fed either a Cu-adequate (Cont; 7.5 micrograms Cu/g diet) or a low Cu (Low; 1.1 micrograms Cu/g diet) casein-based diet for 23 d. Two weeks following initiation of the dietary treatment, each rat was injected intramuscularly (im) with 11.2 microCi of 67Cu. Urine and feces were collected daily. On the 9th d following isotope injection, rats were killed and tissues collected. Significant dietary effects were observed in the relative absorption and endogenous fecal excretion of 67Cu. The tissue distributions of nonisotopic Cu and 67Cu activity were also different between dietary treatments. Tissues from rats fed the low-Cu diet typically had high concentrations of 67Cu and low concentrations of nonisotopic Cu compared to controls. An increase in relative 67Cu absorption was evident for rats fed the low-Cu diet (57.2 and 39.3%, for SD Low, Zucker Low, respectively, and 17.9, and 28.5% SD Cont and Zucker Cont, respectively). Rats fed the low-Cu diet also had reductions in endogenous fecal excretion of 67Cu compared to their respective controls. Although strain effects were not evident for either percent Cu absorption or endogenous fecal Cu excretion, the relative adaptive changes appeared more marked for the Sprague-Dawley rats compared to the lean Zucker rats.

Analysis of Variance↗
PubMed1996

Improved quality of life in patients with generalized cardiovascular metabolic disease on a prepared diet.

Current dietary recommendation for cardiovascular disease risk reduction and recommended dietary allowances (RDAs) were used to develop a nutritionally complete prepackaged prepared meal plan specifically designed to reduce the risk of cardiovascular disease. In the current study we tested patient acceptance of the diet as defined by measures of quality of life. In a randomized, parallel-design, multicenter clinical trial, 77 persons with hypertension, diabetes mellitus, dyslipidemia, or a combination of two or more of these conditions were recruited and randomly assigned to either a prepared meal plan (n = 39) or a comparable self-selected diet (n = 38) for 10 wk. The prepared meal plan met both the RDAs for all essential micronutrients and the dietary recommendations of national health organizations for macronutrients, cholesterol, sodium, and fiber. The prescribed self-selected diet was matched for macronutrients. Quality of life, as measured by a battery of instruments, was the major endpoint. Individuals consuming the prepared meal plan had significant improvements in mental health (P < 0.01), general perceived health (P < 0.005), daily activities (P < 0.05), work performance (P < 0.005), affect (P < 0.01), and nutritional health perceptions (P < 0.001), and reductions in nutrition hassles based on a standardized questionnaire (P < 0.001). The self-selected-diet group had significant improvements in nutritional health perceptions (P < 0.001) and affect (P < 0.001). There were significant improvements in weight (P < 0.001), blood pressure (P < 0.001), cholesterol (P < 0.002), low-density lipoproteins (P < 0.001), glucose (P < 0.014), and glycated hemoglobin (Hb A(1c) (P < 0.004) that were comparable in both groups. In summary, this study shows that a nutritionally complete diet, whether prepackaged or self-selected, improves multiple risk factors for cardiovascular disease. The prepackaged prepared meal plan had the added benefit of a greater improvement in quality of life.

Blood Glucose↗
PubMed1996

Hypothalamic monoaminergic activity in obese Zucker rats in response to acute and chronic dietary stimuli.

Monoamine neuromodulators link diet-related signals with autonomic responses in the regulation of energy balance. In view of evidence that sympathetically mediated expenditure is blunted in genetically obese (fa/fa) Zucker rats, a central defect in neurochemical activity has been proposed. This study tested the hypothesis that genotypic differences in monoaminergic activity in the hypothalamus underlie a blunted sensitivity of fa/fa rats to acute and chronic dietary stimuli, leading to less effective modulation of energy metabolism. Homozygous lean and obese Zucker rats were fed a protein-restricted (PR, protein = 8% of total dietary energy) or control (CF, 21% protein) diet from the age of 5 wk. At 10 wk of age, postprandial oxygen consumption (thermic effect of food, TEF) and levels of brown adipose tissue (BAT) uncoupling protein were significantly elevated (P < 0.0005) in PR vs. CF lean rats. Serotonin turnover was significantly (P < 0.0014) greater in the ventromedial hypothalamus (VMH) of meal-fed lean PR (vs. CF) rats, consistent with the suggestion that VMH serotonin release stimulates sympathetic outflow and may signal a heightened drive for protein intake. Serotonergic activity, BAT uncoupling protein, and TEF were not elevated in PR obese rats in response to a test meal, supporting the view that activation of sympathetic outflow in response to diet-related stimuli in fa/fa rats is impaired.

Animals↗
PubMed1996

Predominately glucocorticoid agonist actions of RU-486 in young specific-pathogen-free Zucker rats.

Previous studies have demonstrated antiglucocorticoid actions for the progesterone receptor antagonist RU-486. In one study, daily administration of this drug for 2 wk decreased food intake (FI) and body weight gain (delta BW) in obese, but not lean, conventionally housed 5-wk-old female Zucker rats. We recently found that 2-wk administration of RU-486 attenuated delta BW in lean but not obese 12-wk-old male Zucker rats without affecting FI. To examine the actions of RU-486 and its effects on FI and delta BW in young (5 wk old) specific-pathogen-free (SPF) male and female Zucker rats, RU-486 was administered at 30 mg.kg-1.day-1 subcutaneously for 14 days. RU-486 did not affect FI in obese or lean male or female rats. RU-486 increased adrenal weight (P < 0.05) overall and in lean female rats and modestly decreased inguinal fat weight overall and in obese female rats (P < 0.01), suggesting some antiglucocorticoid activity in these animals. However, RU-486 also decreased thymus weight by 18-31% (P < 0.0001), increased plasma glucose by 10-16 mg/dl (P < 0.002), and increased plasma insulin by 47% in obese male rats (P < 0.028), demonstrating glucocorticoid agonist actions for the drug. Plasma corticosterone (B) and adrenocorticotropic hormone (ACTH) were elevated in vehicle-treated obese female and male rats by 150-360% (P < 0.0025) and 32-38% (P < 0.05), respectively, compared with lean rats. RU-486 treatment lowered the elevated plasma B and ACTH levels in obese female and male rats (both P < 0.02 vs. vehicle), a glucocorticoid agonist effect. We conclude that in young SPF Zucker rats 1) RU-486 administration does not alter FI or delta BW, 2) RU-486 has predominately glucocorticoid agonist actions in several tissues, 3) obese animals have increased hypothalamic-pituitary-adrenal (HPA) axis activity (plasma B and ACTH), and 4) RU-486 administration suppresses the HPA axis in obese rats.

Adipose Tissue↗
PubMed1996

Relationship of plasma leptin to plasma insulin and adiposity in normal weight and overweight women: effects of dietary fat content and sustained weight loss.

Leptin, the product of the human homologue of the ob gene, which is defective in the obese (ob/ob) mouse, may be a humoral regulator of human adiposity. Plasma leptin concentrations were measured by RIA in 19 normal weight [body mass index (BMI) = 24.5 +/- 0.6 kg/m2] and 19 overweight to obese (BMI = 34.7 +/- 1.2 kg/m2) nondiabetic postmenopausal women on sequential controlled weight-maintaining diets containing 31%, 23%, and 14% of energy as fat, each for 4-6 weeks. Thereafter, the subjects ate a very low fat diet (< 15%) ad libitum; plasma leptin and insulin concentrations, BMI, percent body fat (%BF), and resting energy expenditure were determined after 6 and 8 months. Absolute and adiposity-corrected plasma leptin levels were higher in overweight/obese women (37.7 +/- 3.5 ng/mL; 1.01 +/- 0.07 ng.mL-1.%BF-1) than in normal weight women (16.9 +/- 2.2 ng/mL; 0.57 +/- 0.06 ng.mL-1.%BF-1, both P < 0.005 vs. obese), but were not different between the 31%, 23%, and 14% fat diets when body weight was stable. Plasma leptin was highly correlated with BMI (r = 0.81, P < 0.0001), %BF (r = 0.80, P < 0.0001), and fasting plasma insulin (r = 0.61, P < 0.0001). After 8 months on the ad libitum low fat diet, the women had lost an average of 6.9 +/- 1.0% of body mass (-2.0 +/- 0.3 kg/m2, P < 0.0001). In 15 subjects who lost more than 7% of body mass (-12.3 +/- 1.0%), plasma leptin concentrations decreased (-9.6 +/- 1.9 ng/mL, P < 0.0005), and the decrease of plasma leptin per change of adiposity (delta leptin/delta %BF) was greater in overweight/obese women (3.6 +/- 0.5) than in normal weight women (0.9 +/- 0.4, P < 0.01 vs. obese). In 18 other subjects who lost less than 7% of body mass (-2.7 +/- 0.6%), plasma leptin was unchanged (+1.4 +/- 1.4 ng/mL). Overall, the change of plasma leptin was significantly correlated with change of BMI (r = 0.43, P < 0.02), the change of %BF (r = 0.49, P < 0.005), the change of resting energy expenditure (r = 0.40, P < 0.02), and with the change of plasma insulin independently of changes of body adiposity (r = 0.45, P < 0.01). We conclude that plasma leptin concentrations are: 1) not affected by dietary fat content per se; 2) highly correlated with BMI, %BF, and plasma insulin in both overweight/obese and normal weight women; 3) decreased in parallel with plasma insulin after sustained weight loss; and 4) decreased more in overweight/obese than in normal weight women.

Adipose Tissue↗
PubMed1995

Adrenalectomy increases serotonin turnover in brains of obese Zucker rats.

Because adrenalectomy tends to normalize many metabolic abnormalities of obese Zucker rats, we hypothesized that it would also normalize the depressed serotonergic turnover in their ventromedial nucleus (VMN). Lean (Fa/Fa) and obese (fa/fa) male Zucker rats were adrenalectomized or sham operated when 5 wks old and sacrificed at 11 wks. Their brains were frozen, and 13 areas were dissected for HPLC-EC analysis of monoamines and metabolites. Consistent with previous studies, VMN serotonin turnover (indexed by 5-HIAA/5-HT) was lower in obese than lean sham-operated rats. Monoamine and metabolite concentrations were altered in several other brain areas as well. Adrenalectomy reduced percent body fat and elevated VMN serotonergic turnover more in obese than in lean rats. It also stimulated serotonergic turnover in almost every brain area examined. We conclude that in obese Zucker rats: monoaminergic activity is altered in several brain areas involved in regulating energy balance; adrenalectomy normalizes the reduced VMN serotonergic turnover seen in the obese rats; and adrenalectomy results in a generalized increase in central serotonergic turnover. These data are consistent with serotonin's role in inhibiting food intake and enhancing sympathetic stimulation of energy metabolism.

Adrenal Glands↗