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Biomedical subjects

B E Levin

Publications and source records attributed to B E Levin.

At least 127 records · Page 7Linked to original sources
PubMed1986

Metabolic features of diet-induced obesity without hyperphagia in young rats.

Diet-induced obesity (DIO) developed in 1-mo-old male Sprague-Dawley rats over an 8-wk period on a relatively high-fat (16%) high-calorie (4.6 kcal/g) diet (DIO diet). Percent carcass lipid (56%) and body weight gain (15%) were greater, whereas food intake was decreased over the first 3-5 wk in DIO diet-compared with chow-fed controls. Overall, 8-wk body weight gain (15%), percent carcass lipid (26%), and feed efficiency (15%) were greater, but food intake was not increased. Norepinephrine (NE) turnover rate, indicative of organ sympathetic activity, increased in interscapular brown adipose tissue (IBAT; 57-218%), heart (21-44%), and pancreas (25%) during the first 3 wk and remained elevated for the entire 8 wk. IBAT weight (51%) and in vitro lipolytic capacity (68%) increased by 1 wk and brown adipocyte size (43%) by 3 wk; IBAT thermogenic capacity (maximal NE-stimulated in vitro O2 consumption) increased by 5 wk (39%). Plasma insulin levels were similar in both diet groups over the entire 8-wk period. Why DIO diet-fed rats had increased metabolic efficiency is unknown, but activation of IBAT metabolism and thermogenesis failed to prevent the development of DIO.

Adipose Tissue, Brown↗
PubMed1986

Beta-1 receptor is the predominant beta-adrenoreceptor on rat brown adipose tissue.

A new in vitro radioligand binding assay is described for brown adipose tissue using the beta adrenergic antagonist [3H]CGP 12177 (4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazol-2-one). Binding was saturable and stereoselectively inhibited by propranolol. There was 60 to 80% specific binding using either 30 microM l-isoproterenol or 10 microM l-propranolol to define nonsaturable binding. [3H]CGP 12177 was bound to partially purified membranes from collagenase-separated brown adipocytes with a Kd of 0.84 nM, as determined from kinetic studies, and 1.24 +/- 0.13 nM as found by equilibrium binding studies; maximum binding was 14.2 +/- 0.9 fmol/mg of protein. Membranes from whole-pad homogenates had a similar Kd of 1.17 +/- 0.14 nM but twice the maximum number of binding sites (28.5 +/- 4.4 fmol/mg of protein). Intact brown adipocytes had a Kd of 0.55 nM and a maximum binding of 29.4 +/- 1.5 fmol X 10(-6)/cell or 17,700 sites per cell. Competitive binding studies showed about 80% of the binding sites to be of the beta-1 and 20% of the beta-2 subtype. The pA2 values derived from inhibition of isoproterenol-stimulated in vitro oxygen consumption in intact brown adipocytes by the beta-1 selective antagonist metoprolol and beta-2 selective lCl 118551 were in close agreement with their respective K1 values at the beta-1 receptor as derived from competitive binding studies. These data strongly suggest that the beta-1 adrenoreceptor on brown adipose tissue is primarily responsible for the initiation of thermogenesis in this tissue.

Adipose Tissue, Brown↗
PubMed1986

Neurological regulation of body weight.

We have now come full circle, from a consideration of the factors influencing the control of BW regulation to a review of the human disorders in which these control mechanisms no longer function appropriately. Experimental observation in both animals and man has led to the inescapable conclusion that FI, BW regulation, and thermogenesis are controlled in large part by the CNS. In man, the fairly stable regulation of BW within reasonably close bounds strongly suggests that BW is monitored in some way, and that FI and energy expenditure are regulated in response to this afferent set of signals. Certainly, the number of factors are legion which can influence the central integration and the effector mechanisms by which FI and energy expenditure are regulated by the CNS. The most striking observation is the relative precision with which the overall system works and how few are the number of pathological conditions which severely alter the regulation of BW. The most prominent challenges in this field are the identification of both the sensors of the nutritional status, composition and weight of the organism, and of the actual effectors of thermogenesis in mammals. A more complete understanding of these factors should enable us to better control perturbations of BW under pathological conditions.

Animals↗
PubMed1985

Axonal transport of beta-receptors during the response to axonal injury and repair in locus coeruleus neurons.

Injections of the catecholamine neurotoxin, 6-hydroxydopamine, were placed in the ascending locus coeruleus (LC) pathway in the right cerebral cortex of rats partially destroying the noradrenergic projection to the somatosensory cortex. Norepinephrine (NE) levels fell to a nadir of 49% of control over the first 14 days, associated with a 40% increase in the number of beta-adrenoreceptor binding sites (labeled with [3H]dihydroalprenolol; [3H]DHA) in the denervated cortex. Both NE levels and cortical beta-receptor binding returned to control levels by 28 days. Similar changes, of lesser magnitude, also occurred in the unlesioned, left somatosensory cortex. Catecholamine histofluorescence studies supported these findings of denervation and reinnervation of the right cortex over a 3-month period. Anterograde axonal transport of beta-receptors was assessed by measuring the accumulation of beta-receptor binding sites ([3H]DHA) behind a second lesion placed in the more proximal portion of the ipsilateral LC pathway. Anterograde transport was completely blocked at 4 days, during the initial fall of NE levels, then was increased to 200% of control at 14-21 days, when recovery of cortical NE levels was beginning, and then returned towards control levels by 2-3 months when normal NE levels had been restored.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Clonidine effects on catecholamine levels and turnover in discrete hypothalamic and extra-hypothalamic areas.

In rats treated with alpha-methyl-p-tyrosine (alpha-MpT) or saline, the effects of clonidine on the levels and turnover of norepinephrine (NE), epinephrine (EPI) and dopamine (DA) were analyzed in microdissected regions of the hypothalamus and extra-hypothalamic structures. In 7 of the 9 brain sites examined (namely dorsomedial nucleus, ventromedial nucleus, medial preoptic area, midlateral perifornical hypothalamus, frontal cortex, dorsal hippocampus and cerebellum), clonidine (50 micrograms/kg) caused a significant decrease in NE turnover, with no change in steady-state levels. In the two remaining areas, namely the hypothalamic paraventricular nucleus and the locus coeruleus, clonidine produced different patterns of effects. In the paraventricular nucleus (PVN), clonidine significantly reduced NE content in saline-treated rats, and in rats injected with alpha-MpT + clonidine, no further change in NE concentration was observed. In the locus coeruleus, both NE levels and turnover were unaltered. Epinephrine and DA turnover, in contrast to NE turnover, was unaffected by clonidine in all brain areas, with the exception of the midlateral hypothalamus, where the alpha-MpT-induced depletion of EPI and DA was totally reversed by clonidine, and in the frontal cortex, where DA turnover was also significantly reduced. These data are discussed relative to the proposed physiological actions of clonidine in the hypothalamus.

Animals↗
PubMed1985

Changes in lipid metabolism in diet-induced obesity.

Mature male Sprague-Dawley rats fed a powdered Purina Chow diet containing corn oil and condensed milk (CM) were compared to rats fed a Purina Chow diet (control). CM rats gained more weight and consumed more calories over a 73-day period than the control rats. The increased weight gain and body fat in CM rats was accompanied by increased cell number in retroperitoneal and inguinal but not epididymal fat pads while cell size was unchanged in all three pads. After obesity had developed there was an increase in insulin levels, lipolysis, hepatic fatty acid synthesis, and fatty acid oxidation. While CM rats demonstrated hyperinsulinemia and hyperglycerolemia, they maintained normal glucagon and glucose levels. They demonstrated higher rates of fatty acid synthesis in isolated hepatocytes but not in vivo, suggesting that a greater potential for fatty acid synthesis in CM rats was masked in vivo by the inhibitory action of dietary lipids. Beta-oxidation of (1-14C) palmitate in vivo and in vitro, and in vivo ketogenesis were greater in CM than in chow fed rats. These studies demonstrate that, after the development of obesity, CM rats, like genetically obese Zucker rats, are hyperinsulinemic and have elevated levels of fatty acid synthesis. However, unlike obese Zucker rats, CM rats displayed an increase in beta-oxidation. These studies suggest that increased insulin levels and hepatic fatty acid synthesis may contribute to dietary obesity (as they do to genetic obesity), whereas increased fatty acid oxidation in dietary obesity may be a compensatory response to maintain a lower body weight.

Adipose Tissue↗
PubMed1985

Brown adipose and metabolic features of chronic diet-induced obesity.

Half of the 3-mo male Sprague-Dawley rats fed a high-fat (DIO) diet for 5 mo became obese and had increased carcass lipid (106%) and plasma insulin levels (61%), despite 8% less total energy intake than chow-fed controls. Their interscapular brown adipose tissue (IBAT) was 52% heavier with 45% more lipid and larger uni- and multilocular cells. Norepinephrine turnover was normal in their hearts, pancreases, and aortas but undetectable in IBAT where in vitro lipolysis, but not O2 consumption (VO2), was enhanced. Half the rats fed the DIO diet ate 17% fewer calories, gained weight equally to controls, but still had 34% more carcass lipid. Their IBAT was heavier, contained 103% more protein, with no detectable norepinephrine turnover, whereas maximal lipolysis was 73% lower and maximal VO2 was the same or even lower than controls. IBAT VO2 was stimulated by switching 8-mo chow-fed controls to the DIO diet for 7 days (which caused a 480% greater weight gain) but not by switching 8-mo obese rats to chow for 3 days. Therefore metabolic efficiency was increased while BAT VO2 and norepinephrine turnover were unchanged or reduced compared with controls by either chronic obesity or a high-fat diet.

Adipose Tissue, Brown↗
PubMed1985

Visceral predictors of cardiovascular deconditioning in late middle-aged men.

A major task for space biologists is to try to delineate methods which can be used to predict the degree of cardiovascular deconditioning that given individuals might develop while in space. Toward that end, we have studied a number of different visceral and behavioral variables in a group of late middle-aged men (55-65 years) on day 1 and day 5 of a bedrest regimen. During each 8-h study period, data were collected every 15 min. Mean arterial blood pressure and plasma cortisol and norepinephrine concentrations were significantly higher on the day 5 than on the day 1 of bedrest; heart rate, core temperature, plasma epinephrine and subjective arousal were unchanged. Pair-wise correlations between each of these variables and the time to blackout on a +3-Gz test of acceleration tolerance administered on day 9 of bedrest (mean decrease in latencies from prebedrest was 52%) revealed a significant correlation for the mean arterial blood pressure variable. Thus, these data indicate that men in this age span with relatively low resting blood pressures are at greater risk for developing clinical signs relating to their cardiovascular deconditioning than other men with higher basal blood pressures.

Acceleration↗
PubMed1984

Reserpine and the role of axonal transport in the independent regulation of pre- and postsynaptic beta-adrenoreceptors.

The response of pre- and postsynaptic beta-adrenoreceptors to depletion of brain norepinephrine (NE) with reserpine in the rat was characterized by studying the anterograde and retrograde axonal transport of presynaptic receptors and the receptor binding changes induced in postsynaptic frontal cortex cells. Anterograde transport was shown to occur by the linear accumulation of [3H]dihydroalprenolol ([3H]DHA) binding sites (by in vitro binding assay) proximal to a 6-hydroxydopamine (6-OHDA) lesion placed in the ascending pathway of the locus coeruleus and was blocked by more proximal lesions in the pathway. Retrograde transport was demonstrated by the accumulation of [125I]iodocyanopindolol binding distal to similar lesions. Autoradiograms from sections of 6-OHDA injected brains were produced with [3H]DHA binding in the presence of the beta 2-agonist, zinterol, and suggested that the anterograde accumulation of binding sites was primarily of the beta 1-subtype. A single injection of reserpine (5 mg/kg, i.p.) produced a long lasting (6-8 weeks), biphasic decrease in cortical NE levels with nadirs and 4 and 28 days (10% and 45% of control, respectively). Frontal cortex binding of [3H]DHA increased to a maximum at 7-14 days and again at 28 days post-reserpine (230% and 167% of control, respectively). These increases were not prevented by the destruction of presynaptic noradrenergic nerve terminals with intraventricular administration of 6-OHDA 1 day prior to sacrifice and therefore appeared to take place solely in postsynaptic cells. Presynaptic, anterograde axonal transport of beta-receptors was completely blocked from 4-14 days post-reserpine, increased to 323% of control at 21 days, was blocked again at 6 weeks and returned to control by 8 weeks. Retrograde transport of beta-receptors followed a similar pattern suggesting that the presynaptic alterations in beta-receptors in noradrenergic neurons of the locus coeruleus take place independently from those in postsynaptic cortical beta-receptors as a response to NE depletion by reserpine.

Afferent Pathways↗
PubMed1984

Retrograde axonal transport of beta-adrenoreceptors in rat brain: effect of reserpine.

Retrograde axonal transport of beta-adrenoreceptors was assessed by measuring the accumulation of binding sites for the beta-receptor ligand [125I]iodocyanopindolol [( 125I]ICP) distal to a unilateral 6-hydroxydopamine (6-OHDA) lesion placed in the ascending noradrenergic axons of the locus coeruleus. Accumulation of binding sites was linear over a 3 day period and was blocked by intracerebroventricular 6-OHDA given 1 day prior to sacrifice. A single dose of reserpine (5 mg/kg, i.p.) caused a long lasting (6-8 week) biphasic depletion of frontal cortex norepinephrine (NE) associated with increased frontal cortex binding of another beta-receptor ligand, [3H]dihydroalprenolol [( 3H]DHA), at 7-14 days, and again at 28 days post-reserpine. Unlike the changes in cortical beta-receptors, retrograde transport of [125I]ICP in presynaptic noradrenergic neurons was decreased or blocked completely at 7-14 days and at 6 weeks, and was increased to 470% and 240% of control at 21 days and 8 weeks after reserpine. Anterograde transport of [3H]DHA binding sites was measured by accumulation proximal to a 6-OHDA lesion in this pathway. This transport varied in a pattern similar to that seen for retrograde transport of [125I]ICP binding sites. These data and others suggest that presynaptic beta-receptors are regulated independently of frontal cortex beta-receptors, which appear to be located primarily on postsynaptic cells. On the other hand, the regulation of both anterograde and retrograde transport appears to be interrelated since both types of transport were altered in a similar way in the face of long-term NE depletion by reserpine.

Animals↗
PubMed1984

Central activation and peripheral function of sympatho-adrenal and cardiovascular systems in the Zucker rat.

Electrical stimulation of the hypothalamus in anesthetized lean and obese Zucker rats produced equivalent activation of the sympatho-adrenal system (assessed by plasma norepinephrine [NE] and epinephrine [E] levels) and cardiovascular systems (assessed by monitoring intra-arterial blood pressure and heart rate). Basal plasma E levels were 11% higher and basal heart rates were 20% higher in obese than lean rats. Binding of beta-adrenergic antagonist, [3H] dihydroalprenolol to cardiac membranes was equal but there was a slightly lower affinity for various adrenergic agonists in the hearts of obese compared to lean rats. These results suggest that there are no striking abnormalities in the central pathways for activation of the sympatho-adrenal and cardiovascular systems of obese Zucker rats comparable to those previously described in the peripheral sympatho-adrenal system and other specific organs of these animals [8, 9, 12-15].

Adrenal Glands↗
PubMed1984

Effects of diet and obesity on brown adipose metabolism.

The effect of diet-induced obesity on interscapular brown adipose tissue (IBAT) was assessed after feeding male Sprague-Dawley rats a high-fat diet for 3-5 mo beginning at 3 mo of age. IBAT pads in 6-mo-old obese rats were heavier (22%), had more lipid (71%), and larger unilocular cells (38%) than chow-fed controls. Mitochondrial morphology, beta-adrenergic receptor binding ([ 125I]iodocyanopindolol), and norepinephrine-stimulated lipolysis were similar in IBAT from obese and control rats. When 8-mo-old chow-fed rats were switched to the high-fat diet for 7-14 days, IBAT pads became hypercellular without cell hypertrophy and with a 70% increase in norepinephrine-induced lipolysis. However, when 8-mo-old obese rats that had been on the high-fat diet for 5 mo were switched to chow for 3 days, IBAT cellularity was unchanged, but norepinephrine-induced lipolysis was increased 70%. Therefore, in lean and obese 6- to 8-mo-old rats, short-term dietary manipulation led to metabolic activation, whereas chronic diet-induced obesity on a stable diet was associated with a return of IBAT metabolism to control levels.

Adipose Tissue↗
PubMed1984

Defective brown adipose oxygen consumption in obese Zucker rats.

The thermogenic capacity and morphologic characteristics of interscapular brown adipose tissue (IBAT) were assessed in 3- to 4-mo-old male, lean and obese Zucker rats. Pads from obese rats were threefold heavier and contained similar numbers of cells but an average of 50% fewer multilocular cells than pads from lean rats and 40% less mitochondrial protein per pad. The maximal number of beta-adrenoreceptor binding sites, as assessed by [125I]iodocyanopindolol binding to isolated brown adipocytes from obese rats was 50% of that in lean rats on a per cell and per pad basis. Basal and norepinephrine (NE)-stimulated in vitro oxygen consumption in isolated brown adipocytes from lean rats correlated directly with the proportion of mutilocular cells present. This correlation was not seen in cells from obese rats that had a 50% decrease in their basal respiratory rates and could not be further stimulated by excess NE or fatty acid. Electron micrographs of IBAT from obese rats revealed distorted mitochondrial shapes and cristae patterns and the presence of numerous inclusion bodies. Because NE-stimulated lipolysis had previously been shown to be normal in the obese Zucker rat, these data suggest that defective BAT thermogenesis in the obese rat is due to an inability of mitochondria to utilize free fatty acids for the production of enhanced oxygen consumption.

Adipose Tissue, Brown↗
PubMed1984

Dietary obesity and neonatal sympathectomy. I. Effects on body composition and brown adipose.

The effect of neonatal sympathectomy with guanethidine (50 mg/kg for 3 wk) on the development of diet-induced obesity (DIO) was assessed by raising guanethidine-(G) or saline-treated (S) Sprague-Dawley rats in small litters (4-5 pups/dam) and feeding a high-calorie diet from weaning (n = 29-30) or by raising similarly treated rats in normal litters (10 pups/dam) and feeding chow from weaning (n = 29-30). Sympathectomy depleted norepinephrine (NE) levels 65-98% in all organs except the adrenals and brain but had no statistically significant effect on weight gain, food intake, food efficiency, body composition, plasma glycerol, insulin, or glucose, or on basal rectal temperatures in either diet group; there was a tendency toward increased adiposity in sympathectomized rats. Despite 95-98% depletion of NE in interscapular brown adipose tissue (IBAT), sympathectomy affected only the percentage of multilocular cells that was decreased 46-69%. Rats from small litters in both treatment groups (S and G) became obese without increased food intake (increased food efficiency), had heavier IBAT pads with bigger cells and more lipid, and were also hyperlipidemic, hyperinsulinemic, and hyperglycemic compared with controls. Therefore neonatal sympathectomy was not as significant in the subsequent development of DIO as were diet and litter size.

Adipose Tissue↗
PubMed1984

Dietary obesity and neonatal sympathectomy. II. Thermoregulation and brown adipose metabolism.

Neonatal sympathectomy with guanethidine (50 mg/kg for 3 wk) in Sprague-Dawley rats was previously shown not to significantly affect body weight gain, even when rats were raised in small litters and fed a high-calorie diet from weaning to produce diet-induced obesity (15). In our study rectal temperatures of cold-stressed (24 h at 4 degrees C) sympathectomized rats (obese and lean) fell only 1.4 degrees C after 4 h and were normal by 24 h, as were plasma catecholamine, glycerol glucose, and insulin levels after 4 h at 4 degrees C. Obese rats (with or without sympathectomy) had decreased 4-h (at 4 degrees C) plasma norepinephrine (NE) and increased basal and 4-h plasma glycerol, glucose, and insulin levels. Despite greater than 95% depletion of interscapular brown adipose tissue (IBAT) NE in sympathectomized rats, there was no alteration in beta-adrenoreceptor binding and only 10 and 32% decreases in basal and maximal NE-stimulated O2 consumption, respectively. Obese rats had significant increases in IBAT beta-receptor binding (148-190%/cell, 77-155%/pad) and in basal (11-19%) but not maximal O2 consumption. These results suggest that factors other than the sympathetic nervous system can effectively control thermoregulation, IBAT metabolism, and body weight in the presence of a chronic defect in sympathetic function.

Adipose Tissue, Brown↗
PubMed1984

Regulation of thermogenesis in obesity.

Obesity results when the intake of energy exceeds that which is expended with the resultant storage of the excess energy as fat. Thermogenesis, the metabolic expenditure of energy as heat, is the primary way in which mammals loss dietarily-derived energy and some evidence suggests that certain obese humans may have defective diet-induced thermogenesis. The sympathetic nervous system is the primary effector of thermogenesis through the release of norepinephrine at its nerve terminals. During the early stages of over-eating, there is an increase in sympathetic activity in several organs, including brown adipose tissue (BAT), a major thermogenic organ in many mammals. This increased neural activity is associated with increased thermogenic capacity of the entire animal as well as in BAT and, together, these events are sufficient to prevent the development of obesity in certain young animals such as rats. However, in older rats, obesity eventually develops over several months' of exposure to high energy diets and the early increases in thermogenic capacity and sympathetic activity return to or below baseline levels. Also, genetically obese rodents generally have defective total body and BAT thermogenic capacity, especially to a dietary challenge, as well as abnormal sympathetic function in their BAT. These observations suggest that there are certain types of obesity that are associated with a diminished ability to expend dietarily-derived energy as heat and that chronic obesity in general represents an altered homeostatic state associated with increased metabolic efficiency in some humans and other mammals.

Adipose Tissue, Brown↗
PubMed1983

Alterations of norepinephrine metabolism in rat locus coeruleus neurons in response to axonal injury.

Adult male Sprague-Dawley rats were injected in the right cerebral hemisphere with the neurotoxin 6-hydroxydopamine (6-OHDA) at a site which interrupted the noradrenergic axons ascending from the locus coeruleus (LC). Distal to the injection site ('posterior cortex'), levels of norepinephrine (NE), dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH) fell to 39-42% of control levels ipsilateral to the lesion over the first 25 days, while contralateral levels fell to 32-73% of control during this time. These changes were paralleled by a 63% decrease in the high affinity uptake of [3H]NE in the ipsilateral posterior cortex at 12 days after the lesion. Both ipsilateral and contralateral levels of NE and D beta H fell in the LC during this time, while LC TH showed variable increases and decreases in activity. At 3 months after right cortical 6-OHDA injections, posterior cortical levels of NE, D beta H and TH, as well as the high affinity uptake of [3H]NE, had returned to control levels suggesting that some type of regeneration or axonal sprouting had occurred. Axonal transport of D beta H and TH was assessed by measuring the accumulation of enzyme activity proximal to a 6-OHDA lesion made in the more caudal portion of these same LC axons. Transport of D beta H fell to 7-40% of control from 2 to 24 days and rose to 160% of control by 3 months after the lesion. TH transport was decreased to only 61% of control only at 24 days and returned to control levels by 3 months. These studies document that there is independent regulation of the metabolism of the NE synthetic enzymes, D beta H and TH, during the degeneration and subsequent regeneration or collateral sprouting of injured distal axons of LC noradrenergic neurons.

Animals↗