Altered sympathetic activity during development of diet-induced obesity in rat

1983 ◽  
Vol 244 (3) ◽  
pp. R347-R355 ◽  
Author(s):  
B. E. Levin ◽  
J. Triscari ◽  
A. C. Sullivan

Sprague-Dawley rats developed diet-induced obesity (DIO) after 3 mo on a high-fat, high-sucrose diet (DIO diet), with associated increases in total body and interscapular brown adipose tissue (IBAT) lipid content. After 7 days on the DIO diet, rats had increased levels of tyrosine hydroxylase (TH; 34%), norepinephrine (NE; 34%), and NE turnover (94%; estimated by alpha-methyl-p-tyrosine inhibition of TH) in their IBAT compared with chow-fed controls. After 3 mo on the DIO diet, NE levels and/or turnover were reduced by 27–50% in aortas, hearts, and pancreata in obese rats. While IBAT NE turnover was normal, TH inhibition failed to increase the lipid content of IBAT in obese rats as it did in controls, suggesting a postsynaptic defect in basal NE-stimulated lipolysis in this thermogenically active tissue. When obese rats were switched from the DIO diet to rat chow for 3 days, NE levels remained depressed in their hearts (25%) and aortas (14%) but were increased by 36–45% in IBAT, pancreata, and white adipose tissue. NE turnover rates and/or constants were increased by 37–110% in hearts, aortas, pancreata, and IBAT of these obese rats while there were increased IBAT TH (20%) and dopamine-beta-hydroxylase (87%) activities compared with chow-fed controls. Therefore, sympathetic activity varied markedly as a function of both dietary composition and relative body weight during the development of DIO.

1997 ◽  
Vol 272 (2) ◽  
pp. R656-R661 ◽  
Author(s):  
R. H. Migliorini ◽  
M. A. Garofalo ◽  
I. C. Kettelhut

The effect of prolonged fasting on sympathetic activity was examined in rat white adipose tissue (WAT) and, for comparison purposes, in interscapular brown adipose tissue (IBAT). Preliminary experiments showed that 6-hydroxydopamine or tyramine administration to fed animals produced similar reductions in norepinephrine (NE) content of WAT and IBAT. Fasting for 48 h did not affect tissue NE content significantly, but induced a threefold increase in [3H]NE uptake by retroperitoneal and epididymal adipose tissue, contrasting with a 50% reduction in IBAT. Measured with DL-alpha-methyl-p-tyrosine, NE fractional rates of turnover were faster and calculated turnover rates were three times higher in retroperitoneal and epididymal tissue from fasted rats than in tissues from fed controls. In experiments with [3H]NE, although fractional rates did not change significantly, calculated NE turnover also increased in retroperitoneal and epididymal tissue after food deprivation. In contrast, in IBAT, NE turnover either did not change (measured with DL-alpha-methyl-p-tyrosine) or, in the experiments with [3H]NE, decreased significantly after fasting. These and other data suggest that a centrally controlled selective activation of WAT sympathetic fibers contributes to fasting lipolysis.


1984 ◽  
Vol 246 (5) ◽  
pp. E418-E425
Author(s):  
B. E. Levin ◽  
M. B. Finnegan ◽  
E. Marquet ◽  
J. Triscari ◽  
K. Comai ◽  
...  

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.


1985 ◽  
Vol 248 (6) ◽  
pp. R717-R723 ◽  
Author(s):  
B. E. Levin ◽  
M. Finnegan ◽  
J. Triscari ◽  
A. C. Sullivan

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.


1985 ◽  
Vol 248 (1) ◽  
pp. E20-E25 ◽  
Author(s):  
M. Saito ◽  
Y. Minokoshi ◽  
T. Shimazu

The interscapular brown adipose tissue (IBAT) from obese rats with lesions of the ventromedial hypothalamus (VMH) was approximately 5 times heavier than those from controls. This hypertrophy of IBAT was associated with a marked enlargement of constituent adipocytes and their apparent transformation from multiloculated structure of lipid droplets into the uniloculated structure. The rate of fatty acid synthesis in IBAT of the obese rats was less than one-tenth of that in control rats and approximated the value in white adipose tissue (WAT) when they were starved for 24 h. When rats were fed, the synthetic rate was increased, but the lipogenic response of IBAT in the obese rats was much greater than that in controls, the extent of the response being comparable to that of WAT. The IBAT temperature rose rapidly on electrical stimulation of the sympathetic nerves to the tissue in control rats, whereas the temperature response was reduced markedly in the obese rats. It was suggested that thermogenesis in BAT was impaired in obese rats with VMH lesions by decreasing triglyceride turnover in BAT, probably due to dysfunction of the sympathetic nervous system and a consequent transformation of BAT into WAT.


Author(s):  
O. Kalmukova ◽  
Y. Leonova ◽  
O. Savchuk ◽  
N. Skrypnyk ◽  
M. Dzerzhynsky

One of the prominent obesity-related changes is the development of systemic low-grade proinflammatory state. Brown adipose tissue (BAT) may serve as a potential target for activation by melatonin to facilitate heat production and simultaneously stimulate lipolysis during obesity development. At the same time, melatonin is known to have immunomodulatory properties, which are performed via endocrine and paracrine signal pathways in variety cell types (including brown adipocytes)and change significantly during the day. Therefore, it can be used in a wide range of doses and at different times of the day (chronotherapeutic approach). Thus, the main goal of our research was to analyze the inflammation state of brown adipose tissue of rats during high-calorie diet induced-obesity development after different daily melatonin application in different regimes. Melatonin was administered by gavage for 7 weeks in dose 30 mg/kg 1 h before lights-off (HCD ZT11, M ZT11, evening), or 1 h after lights-on (HCD ZT01, M ZT01, morning). Tissue collagen content and leukocyte infiltration levels in BAT, detected by Van Gieson trichrome staining, were used as markers for the assessment of BAT inflammation state BAT. Propagation of obesity resulted in the increase of BATfibrosis level (the relative area occupied by collagen fibers) and tissue leukocyte infiltration in comparison to control rats. BAT fibrosis level after melatonin administrations to obese rats of HCD ZT01 and HCD ZT11 groups decreased to control values. Similar effects were observedinBAT tissue leukocyte infiltration after both regimes (HCD ZT01 and HCD ZT11 groups) of melatonin intake: this parameter decreased significantly, comparing to obese rats, but was still elevated, comparing to controls. At the same time, melatonin treatmentin morning or evening regimes did not have any impact on BAT fibrosis propagation and leukocyte infiltration in animals that consumed standard diet (M ZT01 and M ZT11 groups). To sum up, we suggest corrective properties of melatonin in context of chronic low-grade inflammation in obese rats BAT and suppose its wide potential for the therapeutic use combined with virtually absent side effects on BAT histophysiology of non-obese rats.


1994 ◽  
Vol 143 (3) ◽  
pp. 433-439 ◽  
Author(s):  
T H M Da Costa ◽  
D H Williamson ◽  
A Ward ◽  
P Bates ◽  
R Fisher ◽  
...  

Abstract Transgenic mice were made by introducing extra copies of the mouse insulin-like growth factor-II (IGF-II) gene driven by the bovine keratin 10 promoter (BKVI). The adult plasma IGF-II levels were elevated at least three times in one line. In this line, there was a lower lipid content of both brown and white adipose depots at 2–4 months of age, and 40% less fat in the carcass at 7–9 months. The low lipid phenotype was not detected in the carcass at 2 weeks after birth. The lean characteristic was attributed to circulating IGF-II because the transgene was not expressed in fat. At 2–4 months of age, the transgenes oxidized more oral lipid, and less of this lipid was incorporated into the whole body and the epididymal fat. In contrast, the interscapular brown adipose tissue maintained lipid incorporation and lipoprotein lipase activity despite its reduced size. The altered activity of the brown adipose tissue may account for the gradual onset and persistence of the lean feature of the transgenic mice. There were no substantial changes in lipogenesis which could account for the low fat content. The plasma levels of IGF-I, insulin, glycerol, non-esterified fatty acids, triacylglycerols and glucose were not greatly changed and the pituitary GH content was within the normal range. Journal of Endocrinology (1994) 143, 433–439


1994 ◽  
Vol 266 (3) ◽  
pp. E453-E458 ◽  
Author(s):  
L. A. Cassis

Previous studies demonstrated that interscapular brown adipose tissue (ISBAT) produces angiotensin II (ANG II), which facilitates sympathetic neurotransmission (SN). ANG II content and regulation of SN were examined in young (17 days) and adult (16 wk) Zucker obese and lean rats. ANG II content in ISBAT from preobese rats was decreased compared with lean littermates. Evoked 3H overflow in ISBAT slices preloaded with [3H]NE was greater in preobese rats compared with control. ANG II increased evoked 3H overflow in ISBAT slices to a greater extent in preobese rats compared with control. [3H]NE uptake in ISBAT slices from preobese rats was decreased compared with control. In adult obese rats, plasma renin activity was decreased compared with control. ISBAT ANG II content was increased in adult obese rats compared with control. Evoked 3H overflow in ISBAT slices preloaded with [3H]NE was not different between obese and control. ANG II did not increase evoked 3H overflow in obese rats; however, ANG II increased evoked 3H overflow in lean rats. [3H]NE uptake in ISBAT slices from obese rats was decreased compared with control. These results suggest that ANG II modulation of SN activity is decreased in ISBAT from adult obese rats. In contrast, in young obese rats, increased SN activity and ANG II regulation of SN were evident in brown adipose tissue.


1989 ◽  
Vol 257 (6) ◽  
pp. R1377-R1385 ◽  
Author(s):  
M. Egawa ◽  
H. Yoshimatsu ◽  
G. A. Bray

The effects on firing rate of sympathetic nerves to interscapular brown adipose tissue were measured after induction of intracellular glycopenia by peripheral or central administration of 2-deoxy-D-glucose (2-DG). Injection of 2-DG (250 mg/kg body wt) into the jugular vein rapidly suppressed the sympathetic activity, which declined 84% within 10 min after the injection. This suppression persisted for at least 40 min. Hyperglycemia did not affect the sympathetic activity but partially inhibited the suppressive effect of 2-DG injection. Acute vagotomy failed to block the suppressive effect of 2-DG. Injection of 2-DG (2.5 mg/rat) into the third cerebral ventricle suppressed the sympathetic activity. This suppression was followed by gradual recovery. Saline injection did not affect the sympathetic activity. We conclude that cellular glycopenia induced by injecting 2-DG peripherally or into the third cerebral ventricle suppresses the sympathetic activity to brown adipose tissue. The results are consistent with the hypothesis that an acute energy shortage decreases the thermogenesis in interscapular brown adipose tissue by suppressing sympathetic neural activation of this tissue.


Metabolism ◽  
1987 ◽  
Vol 36 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Toshihide Yoshida ◽  
Hitoshi Nishioka ◽  
Keiji Yoshioka ◽  
Motoharu Kondo

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