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Biomedical subjects

J S Stern

Publications and source records attributed to J S Stern.

At least 91 records · Page 5Linked to original sources
PubMed1993

Time-dependent effects of progressive gamma-linolenate feeding on hyperphagia, weight gain, and erythrocyte fatty acid composition during growth of Zucker obese rats.

Obese Zucker rats (fa/fa) have low levels of arachidonic acid (AA) in liver phospholipids (PL). We have previously shown that a 70% gamma-linolenate concentrate (GLA; an AA intermediate) fed at a fixed dose (0.07 g/day) normalized hepatic PL AA and reduced weight gain selectively in the obese animals. In a follow-up study, 16 obese (fa/fa) and 16 lean (Fa/Fa) 4-week-old male rats were randomized into 4 groups of 8 each and gavaged daily with soybean oil (SOY) containing 55% 18:2omega6 (an AA precursor) or GLA, using a progressive dose (< or = 5% of total calories) based on body weight. A defined diet with 11% of energy as SOY was fed ad libitum for 60 days. GLA obese had lower body weight (p<0.0001) and 60-day cumulative food intake (p<0.05) compared to SOY obese, but neither parameter differed between the lean groups. For the last twenty days cumulative food intake was identical for GLA obese and SOY lean, whereas SOY obese consumed 18% more (p<0.05). Thus the progressive dose of GLA selectively suppressed hyperphagia in obese Zucker rats. Erythrocytes collected at 15-day intervals showed parallel increases in AA in both genotypes over time, suggesting normal AA availability during rapid growth. Thus, the reduced PL AA in the livers from the obese rats probably reflects impaired distribution in selected tissues rather than reduced hepatic production. Due to the potential health risks of enriching tissue lipids with AA, great caution is advised in considering GLA as therapy for human obesity.

Adipose Tissue↗
PubMed1993

Abnormal polyunsaturated lipid metabolism in the obese Zucker rat, with partial metabolic correction by gamma-linolenic acid administration.

Below-normal proportions of phospholipid (PL) arachidonic acid (20:4 omega 6) have been reported in serum from obese humans and in liver from obese Zucker rats. This implies an abnormality of 20:4 omega 6 formation from linoleic acid (18:2 omega 6), possibly in the delta 6 desaturase step, or alternatively an abnormality in the catabolism or distribution of arachidonate. We previously speculated that a reduced proportion of 20:4 omega 6 in hepatic PL could contribute to the etiology of genetic obesity. Providing 18:3 omega 6 would bypass delta 6 desaturase and possibly normalize hepatic PL 20:4 omega 6. Therefore weanling Zucker rats were given free access to a defined diet (11% of energy as soy oil) and gavaged daily with 100 microL of either black currant oil concentrate ([BCO] 8% 18:2 omega 6 and 70% 18:3 omega 6) or soy oil ([Soy] 55% 18:2 omega 6 and < 0.1% 18:3 omega 6). Groups of eight lean and eight obese animals were randomized to receive Soy or BCO in a 2 x 2 design; 10 obese and 10 lean rats were fed a stock diet (nongavaged reference). All groups of lean rats had identical weight gain; food intake for Soy lean and BCO lean did not differ. The obese reference animals and Soy obese animals did not differ in weight gain. However, BCO obese animals ate less food (P < .06), gained less weight (P < .0001), and had lower percent body fat (P < .05) compared with the Soy obese animals. The fatty acid constituents from serum, liver, and adipose tissue showed marked differences between lean and obese animals. Hepatic PL 20:4 omega 6 was lower in Soy obese than in lean (P < .002), but was normalized by BCO gavage (diet effect, P < .007). The paucity of hepatic PL 20:4 omega 6 was not due to reduced desaturase activity, as the proportions of other desaturase products (20:3 omega 6, 20:3 omega 9, 20:5 omega 3) were significantly elevated in Soy obese rat liver and serum. Serum and hepatic cholesteryl ester 20:4 omega 6 levels were elevated in obese versus lean rats (P < .02 and P < .0001), indicating abnormal arachidonate distribution in the obese Zucker rat. Because BCO selectively reduced weight gain and percent body fat in obese Zucker rats, our results imply a role for abnormal omega 6 fatty acid metabolism in the etiology of Zucker obesity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1993

Effect of age and high sucrose diet on 2-deoxyglucose uptake in perfused hindlimb.

The purpose of this investigation was to evaluate insulin-stimulated skeletal muscle glucose uptake in male Fischer 344 rats, age 6, 12, and 27 mo, fed either a sucrose (S: 66.6% sucrose, 17.6% protein, 6.4% fat) or sucrose-free (SF: 66.6% starch, 17.6% protein, 6.4% fat) diet for 3 mo. Skeletal muscle glucose uptake (Rg) in perfused hindlimbs was estimated from the uptake and subsequent phosphorylation of radiolabeled 2-deoxyglucose (2DG) in the gastrocnemius (GN), extensor digitorum longus (EDL), and soleus (SOL) muscles. Rat hindlimbs were perfused at a rate of 10 ml.min-1 with a modified Krebs Henseleit buffer containing bovine red blood cells (hematocrit: 40%) and 5.85 mmole.L-1 glucose along with 358 pmoles.L-1 followed by 3580 pmoles.L-1 insulin. There was no effect of diet on plasma glucose levels measured at weeks 1, 7, and 11 of the dietary period. A significant effect of age on estimated glucose uptake in the GN was demonstrated due primarily to greater uptake in the 27-mo compared to the 6-mo-old animals. This significant effect of age was not evident in the EDL or SOL, nor were there significant effects of diet in any muscle. These data suggest that insulin-stimulated glucose uptake in perfused hindlimbs is not attenuated with senescence or with the feeding of a sucrose diet for 3 months.

Adenosine Triphosphate↗
PubMed1993

Litter size, adrenalectomy and high fat diet alter hypothalamic monoamines in genetically lean (Fa/Fa) Zucker rats.

To determine if diet-induced obesity is associated with depressed serotonergic activity (as is genetic obesity), we examined hypothalamic biogenic amines in 11-wk-old genetically lean (Fa/Fa) male Zucker rats raised in small (3 pups/dam) or control (8-9 pups/dam) litters. Five-week-old rats were adrenalectomized or sham-operated and, 1 wk later, fed either 11% of energy as fat (low fat) or 68% of energy as fat (high fat) diets for 5 wk. Tissue punches from the ventromedial nucleus (VMN), the paraventricular nucleus and the preoptic area were assayed via HPLC. Rats fed high vs. low fat had a greater percentage of body fat and brown fat mitochondrial GDP binding, whereas serotonergic turnover was lower. Small litter vs. control litter animals had lower VMN and preoptic concentrations of 3,4-dihydroxyphenylacetic acid, a major metabolite of dopamine. Although adrenalectomy resulted in smaller, leaner rats, it did not differentially affect the rats that became fatter. Because VMN and preoptic dopaminergic activities were depressed in small litter vs. control litter rats but the percentage of body fat was unchanged, this decreased dopamine metabolism is probably not causal to the obesity development. However, the same cannot be said for the attenuated serotonergic activity, although such activity may not be directly related to the degree of obesity.

Adipose Tissue↗
PubMed1993

Autonomic control of pancreatic polypeptide and glucagon secretion during neuroglucopenia and hypoglycemia in mice.

Neural control of pancreatic polypeptide (PP) release has not been previously investigated in the mouse. In addition, it is not known to what extent increased glucagon secretion during hypoglycemia in mice is neurally mediated vs. an effect of hypoglycemia to directly stimulate glucagon secretion at the level of the islet. Feeding or the cholinergic agonist carbachol increased plasma PP levels in conscious mice (+74 +/- 18 pg/ml vs. fasted mice and +141 +/- 17 pg/ml vs. control, respectively). Neuroglucopenia induced by 2-deoxy-D-glucose or insulin-induced hypoglycemia also increased plasma PP (+79 +/- 18 and +89 +/- 11 pg/ml vs. control, respectively). These increases were abolished by hexamethonium and reduced by atropine methylnitrate (atropine). Hypoglycemia-induced hyperglucagonemia (+1,243 +/- 275 pg/ml) was reduced to 31 +/- 7% of control by atropine (+382 +/- 85 pg/ml), to 48 +/- 9% of control by combined adrenergic blockade (+601 +/- 112 pg/ml), and nearly abolished by atropine plus combined blockade (+143 +/- 41 pg/ml; 11 +/- 3% of control) or hexamethonium (+151 +/- 38 pg/ml; 12 +/- 3% of control). We conclude the following in the mouse. 1) Feeding or cholinergic agonists increase plasma PP. 2) During neuroglucopenia or hypoglycemia, plasma PP is increased via nicotinic and muscarinic mechanisms. 3) The glucagon response to hypoglycemia is predominantly the result of autonomic activation and is mediated by both muscarinic and adrenergic mechanisms.

Animals↗
PubMed1993

Obesity. Workshop III. AHA Prevention Conference III. Behavior change and compliance: keys to improving cardiovascular health.

The workshop provided the opportunity to discuss issues and develop and integrate ideas. The following recommendations for public policies, education programs, and high-priority research initiatives were developed: Recommendations for Public Policies: Focus on prevention by requiring school programs to emphasize appropriate diet, physical activity, and general health guidance to promote cardiovascular health and prevent disease through federal funding. Provide better access to exercise (city planning, work-site interventions). Influence food availability and accessibility. Influence reimbursement policies for effective early intervention and prevention strategies for obesity. Reevaluate policies for use of drugs in the treatment of obesity. Recommendations for Education Programs: Sponsor scientific workshop to: Define the most appropriate weight standards for prevention and treatment. Identify who should lose weight and why, when, and how. Promote the fact that obesity is an important health risk factor, even at moderate levels, and that excess visceral fat is particularly hazardous. Target health care professionals, consumers, and the media for education about: Nature of obesity as a heterogeneous syndrome. Recommendations for diet, exercise, behavioral interventions, drugs, and surgery. Recognition of special needs of populations of different ethnicity, gender, age, etc. State-of-the-art treatment and treatment programs. High-Priority Research Initiatives: Build better bridges between basic research and treatment/prevention practices. Acknowledge that obesity is a heterogeneous syndrome that may best be characterized as different obesities. Research on defining subtypes. Implications for etiology and treatment. Better characterization of genotypes and phenotypes. Study the effects of weight loss, weight gain,and weight cycling on medical and psychosocial outcomes and mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Selective muscarinic sensitivity in perfused pancreata of obese Zucker rats.

Insulin secretion was evaluated in response to the muscarinic agonist, bethanechol, and to the antagonist, atropine, in three-month-old female homozygous lean (Fa/Fa) and obese (fa/fa) Zucker rats, using an in vitro pancreas perfusion. Three doses of bethanechol were used (0.5, 5 or 50 microM). Bethanechol at 50 microM concentration had a significant potentiating effect on glucose-induced insulin secretion in pancreata from both lean and obese rats. There was no effect of atropine (25 microM) on insulin secretion in pancreata from either lean or obese rats. In another study, the perfusate used contained glucose at 75, 125 or 200 mg/dl for the entire 60 min period. Perfusate, with or without bethanechol (50 microM), was infused from 21-40 min, using a side-arm syringe. In general, bethanechol significantly increased insulin secretory rates in both lean and obese rats. Since the pancreas of obese rats secretes more insulin to the same glucose concentration than the pancreas of lean rats, we compared changes in insulin release due to bethanechol in obese and lean rats having comparable basal insulin secretory rates during the 11-20 min period. To produce comparable insulin secretion, glucose levels in the perfusate were kept lower in the obese group (75 mg/dl). In the comparably secreting lean group, a glucose level of 200 mg/dl was required. We also compared changes in insulin secretory rate due to bethanechol stimulation between groups with comparable insulin secretory rates during the 21-40 min period in the control groups, i.e. 75 mg/dl glucose in the obese group vs. 125 mg/dl glucose in the lean group.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Effect of adrenalectomy and high-fat diet on the fatty Zucker rat.

Lean and obese Zucker fatty rats were adrenalectomized or sham operated at 10 wk of age. At 15 wk one-half of each group was placed on a high-fat diet. At 32 wk of age the experiment was ended. Several conclusions can be drawn about the effects of adrenalectomy, high-fat diets, and their interaction in the Zucker fatty rat. First, adrenalectomy slowed the weight gain in both obese fatty rats and in the lean animals, although the effect was greater in the fatty rats. Second, weight gain was accelerated in intact lean and fatty rats eating a high-fat diet. Third, adrenalectomy attenuated the weight gain associated with a high-fat diet and reduced the body content of fat and protein in the lean animals and fatty rats fed the low-fat diet. Fifth, adrenalectomy significantly affected the retroperitoneal and subcutaneous fat depots but not the epididymal fat depot. Sixth, adrenalectomy decreased fat cell number in retroperitoneal and subcutaneous fat depots, but this was much less evident in the epididymal fat depot. Seventh, lipoprotein lipase activity expressed per milligram protein increased after adrenalectomy in the fatty rat but was reduced on the same basis in lean animals regardless of diet. Finally, the increase in retroperitoneal lipoprotein lipase activity expressed per fat cell observed in lean animals fed the high-fat diet was not observed in the fatty rat. These studies show that a high-fat diet and adrenalectomy interact in the development of obesity in both lean and fatty Zucker rats.

Adipose Tissue↗
PubMed1992

Adipose tissue lipolysis in vitro: a predictor of diet-induced obesity in female rats.

Wide ranges in weight and fat gain in response to high-fat diets have been reported in rats. This study measured epinephrine-stimulated lipolysis in adipose tissue of normal weight, 3-mo-old, female Sprague-Dawley rats as a metabolic predictor of "efficient gain" before feeding them a high-fat (84% kcal) diet for 11 wk. Subcutaneous (inguinal) adipose tissue (1-1.5 g) was excised, and the glycerol release was measured after incubation with 0, 10(-7), 10(-5), and 10(-3) M epinephrine. Differences in gain efficiency explained much of the variation in lipid (r = 0.78) and weight (r = 0.83) gain. Low glycerol release by 10(-5) and 10(-3) M epinephrine was significantly correlated to high final fat accumulation. Low and high quartiles based on glycerol release were not different in numbers of adipocytes or food intake but were significantly different in gain efficiency (P = 0.011), final weight (P = 0.036), carcass lipid (P = 0.033), and carcass lean mass (P = 0.017). In conclusion, female Sprague-Dawley rats are preferentially predisposed to efficiency of adipose accumulation on a high-fat diet. This tendency is negatively correlated in the preobese state to the lipolytic response to epinephrine of subcutaneous adipose tissue in vitro.

Adipose Tissue↗
PubMed1992

Autonomic nervous system mediation of the pancreatic polypeptide response to insulin-induced hypoglycemia in conscious rats.

To investigate the neural regulation of pancreatic polypeptide (PP) secretion during hypoglycemia in the rat, insulin was administered to chronically cannulated rats, and plasma PP responses were compared between saline-treated animals and animals pretreated with a ganglionic blocking agent (hexamethonium), a muscarinic antagonist (atropine), combined alpha- and beta-adrenergic receptor blockade (propranolol + tolazoline), or combined adrenergic blockade + atropine. PP was measured using a new RIA which selectively detects PP in rat plasma. In control rats (n = 10), plasma PP increased from a baseline level of 30 +/- 3 pg/ml to 271 +/- 41 pg/ml during hypoglycemia (plasma glucose = 29 +/- 2 mg/dl) (delta PP = +241 +/- 42 pg/ml, P less than 0.0005), demonstrating that in rats, as in other species, insulin-induced hypoglycemia is a potent stimulus for PP release. PP only increased by 31 +/- 10 pg/ml during similar hypoglycemia in 7 hexamethonium-treated rats (P less than 0.01 vs. control animals). Thus, at least 90% of the PP response to hypoglycemia is neurally mediated. The plasma PP response to hypoglycemia was +85 +/- 24 pg/ml in atropine-treated rats (P 0.01 vs. control rats), suggesting that approximately 65% of the PP response is mediated via muscarinic acetylcholine receptors on the islet F cell. The PP response to hypoglycemia in rats with combined adrenergic blockade (delta = +168 +/- 32 pg/ml) was slightly, but not significantly smaller than that in control rats. The combination of combined blockade + atropine resulted in a PP response (delta = +26 +/- 7 pg/ml) to hypoglycemia that was similar to that in hexamethonium-treated rats (P less than 0.01 vs. control rats). These results suggest: 1) The PP response to hypoglycemia is predominantly the result of muscarinic, cholinergic activation. 2) There is a minor adrenergic contribution to the response. 3) The plasma PP response may be useful as an index of autonomic neural input to the islet during hypoglycemia.

Animals↗
PubMed1992

Obese Zucker (fa/fa) rats exhibit normal target sensitivity to corticosterone and increased drive to adrenocorticotropin during the diurnal trough.

Genetically obese Zucker (fa/fa) rats exhibit numerous metabolic and endocrine disorders associated with modest hypercorticosteronemia and reported changes in peripheral target tissue sensitivity to glucocorticoids. In this study we investigated phenotypic differences in basal and stress-induced ACTH and corticosterone (B) secretion in intact and adrenalectomized lean and obese male Zucker rats. In addition, we determined whether differences in the sensitivity to B of plasma ACTH and insulin secretion as well as other peripheral B targets could be observed between the two phenotypes. There were no significant differences in basal ACTH or B in either the morning (AM) or evening (PM) in intact obese and lean rats; however, mean B was increased in the obese rats in the AM, and signs of chronically increased adrenocortical activity were observed, including increased adrenal weight and intraadrenal phenylethanolamine-N-methyl transferase activity and decreased thymus weight. In a second experiment, B was significantly elevated 3 min after either administration in obese compared to lean rats; however, there was no significant difference in B between the groups at 10 min, nor were ACTH levels at these times different. Five days after adrenalectomy with sc B replacement, ACTH was decreased as a function of B in both phenotypes under AM basal and stress conditions. The IC50 values for inhibition of basal ACTH by B were 3.16 and 4.17 micrograms/dl in lean and obese rats, respectively. Under stress conditions, the IC50 values were not different (4.39 micrograms/dl for lean and 4.24 micrograms/dl for obese rats). B dose-dependent increases in body and epididymal fat depot weights were greater in obese than in lean rats, an expected result because of elevated insulin levels in this group. Insulin exhibited only small B-dependent increases, and thymus weight decreased in a B-dependent fashion; there were no differences in the sensitivity to B of these measures between lean and obese rats. We conclude that 1) there is no evidence for altered sensitivity to B in obese rats for any of the B-sensitive end points measured; and 2) basal adrenocortical activity is slightly elevated, and the sensitivity of ACTH to B feedback is decreased in obese rats under AM conditions in the absence of external stress.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1992

Effects of increasing brain GABA on the meal patterns of genetically obese vs. lean Zucker rats.

To explore recent suggestions that genetically obese Zucker rats show less anorexia when brain gamma-aminobutyric acid (GABA) is elevated, obese vs. lean littermates received 100, 50 and 0 micrograms of the GABA-transaminase inhibitor, ethanolamine-O-sulfate (EOS), intra-cisternally in a longitudinal design where their feeding patterns were monitored 24 h daily. Obese rats were refractory to EOS-induced anorexia as evidenced by less suppression of daily food intake and fewer alterations to both meal size and meal frequency, particularly in the night. This effect was not due to an inability of EOS to increase brain GABA since equivalent, specific dose-dependent increments were seen in the brains of separate obese vs. lean rats after analysis of endogenous GABA and seven other amino acids. An unexpected finding was elevated levels of brain taurine for obese rats regardless of EOS dosage, implying a hitherto unknown neurochemical trait whose potential significance is unclear. The primary data obtained provide further support for recent hypotheses that obese Zucker rats possess altered brain GABAergic mechanisms that may serve as one contributor to their over-eating.

Animals↗
PubMed1992

Effect of suspending exercise training on resting metabolic rate in women.

We tested the hypothesis that enhanced resting metabolic rate (RMR) in highly trained endurance athletes is an acute effect of prior exercise induced by catecholamines and not serum thyroxine. RMR and energy-regulating hormones were studied in nine highly trained women runners during habitual training (period I), and suspension of training (period II). Data were collected during the follicular phase of two consecutive menstrual cycles, confirmed by serum progesterone and estradiol. Subjects maintained training between the two periods. Total energy intake and diet composition, body weight, and oral temperature did not change from period I to period II (P greater than 0.05). With suspension of training, urinary epinephrine and nonrepinephrine excretion dropped (P less than 0.022) while serum TSH rose (P = 0.011) and free T4 did not change (P = 0.182). RMR (mean +/- SEM) was 274 +/- 6.2 and 252 +/- 7.8 kJ.h-1 for periods I and II, respectively, with repeated measures ANOVA indicating a drop in RMR occurred with cessation of exercise (P = 0.048). The augmentation of RMR by exercise lasted more than 15 h but less than 39 h post-exercise. The results suggest that the drop in catecholamines may partly explain the lower RMR following suspension of training.

Basal Metabolism↗
PubMed1991

The gene encoding rat liver glycogen phosphorylase contains multiple polyadenylation signal sequences.

RNA blot analysis of rat liver and adipose tissues detected two glycogen phosphorylase (GP)-encoding transcripts. The polymerase chain reaction was used to characterize the 3'-noncoding region of the gene (L-GP) encoding liver-GP (L-GP) from the lean Zucker rat (Fa/Fa). Three distinct classes of colinear cDNA clones were identified by nucleotide (nt) sequence analysis, demonstrating that the L-GP gene contains at least three functional polyadenylation sites. The predominant L-GP transcript was generated by polyadenylation 130 nt 3' from the end of the coding region. A previously uncharacterized L-GP transcript is generated by polyadenylation at 346 nt 3' of the first polyadenylation site. Polyadenylation site selection does not appear to be regulated in a tissue-specific fashion. The relative steady-state L-GP mRNA levels in the different types of adipose tissues were comparable to, or exceeded transcript levels in liver.

Adipose Tissue↗
PubMed1991

Inhibition by cations of antagonist binding to histamine H1-receptors.

The binding of the quaternary radioligand [3H] QMDP to the histamine H1-receptor was inhibited by a series of mono- and di-valent cations. The order of potency was Hg2+ greater than Cd2+ greater than Zn2+ greater than Ni2+ greater than Co2+ greater than Mn2+ greater than Ca2+ greater than Mg2+ greater than Li+ = Na+ greater than K+ greater than Cs+. The binding of [3H] mepyramine, a tertiary amine, was inhibited by the divalent cations to a similar extent as the binding of [3H] QMDP. Li+ also had a similar potency against the two ligands, but Na+ was a much more potent inhibitor of the binding of [3H] QMDP than that of [3H] mepyramine.

Animals↗