Specific decrease of mitochondrial thermogenic capacity in brown adipose tissue of obese SHR/N-cp rats

1993 ◽  
Vol 265 (6) ◽  
pp. C1674-C1680 ◽  
Author(s):  
C. Atgie ◽  
A. Marette ◽  
M. Desautels ◽  
O. Tulp ◽  
L. J. Bukowiecki
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Protein Content ◽  
Cytochrome Oxidase ◽  
Oxidase Activity ◽  
Skeletal Muscles ◽  
Brown Adipose ◽  
Obese Rats ◽  
Thermogenic Capacity

The metabolic properties of brown adipose tissue (BAT), liver, and skeletal muscles were compared in lean and obese diabetic SHR/N-cp rats (a new model of type II diabetes) to test whether the severe insulin resistance of obese animals is specifically associated with a thermogenic defect in BAT. The respiratory response of brown adipocytes to norepinephrine and to agents bypassing the adenylate cyclase complex (dibutyryl cyclic AMP and palmitate) was decreased by two-thirds in obese rats, thereby indicating the presence of a major postreceptor defect. Significantly, total BAT cytochrome oxidase activity, uncoupling protein content, and mitochondrial guanosine 5'-diphosphate binding (3 indexes of BAT thermogenic capacity) were also decreased by two-thirds. The specific activities of these parameters expressed per total BAT mitochondrial protein were not altered either. This indicates that the total number of mitochondria per cell is decreased in BAT of obese rats. In contrast, total tissue cytochrome oxidase activity, protein content, and DNA content all increased by two to three times in the liver of obese SHR/N-cp rats, but these parameters remained unchanged in skeletal muscles (vastus lateralis and soleus). Such a remarkable liver hypertrophy may have occurred as a consequence of the persistent hyperphagia-hyperinsulinemia of obese rats that induced a hyperplasia and/or a hepatocyte polyploidization. This observation together with the fact that daily energy expenditure associated with food intake was markedly increased in obese rats (representing as much as 25% of the total energy expenditure) strongly suggests that the liver plays a major role in energy balance in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonshivering thermogenesis and the thermogenic capacity of brown fat in fasted and/or refed mice

1988 ◽  
Vol 254 (1) ◽  
pp. R11-R16 ◽  
Author(s):  
P. Trayhurn ◽  
G. Jennings
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cytochrome Oxidase ◽  
Oxidase Activity ◽  
Uncoupling Protein ◽  
Nonshivering Thermogenesis ◽  
Interscapular Brown Adipose Tissue ◽  
Cytochrome Oxidase Activity ◽  
Brown Adipose ◽  
Thermogenic Capacity

The effects of fasting and refeeding on nonshivering thermogenesis and the properties of brown adipose tissue have been investigated in mice. Fasting for 48 h led to a substantial reduction in the capacity for nonshivering thermogenesis, and there was no recovery of thermogenic capacity during the first 5 days of refeeding. A period of 10-15 days of refeeding was required for full restoration of thermogenic capacity. The mice were hyperphagic during the first 6 days of refeeding, but body weight was recovered after 24 h. The amount of interscapular brown adipose tissue decreased substantially on fasting, but it recovered 24 h after the initiation of refeeding. Cytochrome oxidase activity, the level of mitochondrial GDP binding, and the specific mitochondrial concentration of uncoupling protein in brown adipose tissue were each reduced by fasting. Although both GDP binding and the specific concentration of uncoupling protein rapidly returned to normal on refeeding, the activity of cytochrome oxidase was not normalized until 10 days after the end of the fast. These results indicate that a prolonged period of refeeding is required for the recovery in the capacity for nonshivering thermogenesis following a fast, a similar time course being evident for the recovery of cytochrome oxidase activity in brown adipose tissue. It is suggested that the fasting-induced reduction in the capacity for nonshivering thermogenesis is linked primarily to a loss of mitochondria from brown adipose tissue and that the normalization of thermogenic capacity is dependent on the restoration of mitochondrial mass.

The Effects of Thyroxine and Isopropylnoradrenaline on Cytochrome Oxidase Activity in Brown Adipose Tissue

1973 ◽  
Vol 51 (10) ◽  
pp. 751-758 ◽  
Author(s):  
H. M. C. Heick ◽  
C. Vachon ◽  
Mary Ann Kallai ◽  
Nicole Bégin-Heick ◽  
J. LeBlanc
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Protein Content ◽  
Cytochrome Oxidase ◽  
Cold Adaptation ◽  
Metabolic Response ◽  
Mitochondrial Enzymes ◽  
Cold Adapted ◽  
Brown Adipose ◽  
Hormonal Treatments

Groups of animals were treated with injections of isopropylnoradrenaline, thyroxine, or both hormones together. The effects of these hormonal treatments on the size, protein content, and level of some mitochondrial enzymes, in particular the cytochrome oxidase, were determined and compared to the effect on these parameters produced by cold adaptation. The changes observed were correlated with the resistance of the animals to cold stress and with their metabolic response to injections of isopropylnoradrenaline. All treatments increased the size of the brown adipose tissue. Whereas thyroxine had little effect on the protein content and cytochrome oxidase, both isopropylnoradrenaline and cold adaptation produced increases in these parameters. It appears that the isopropylnoradrenaline-treated animals mimic more closely the cold-adapted animals than do those with thyroxine treatment. However, the isopropylnoradrenaline-treated animals are not as resistant to cold as the cold-adapted animals.

scholarly journals GDP binding to brown-adipose-tissue mitochondria of mice treated chronically with corticosterone

1983 ◽  
Vol 214 (1) ◽  
pp. 265-268 ◽  
Author(s):  
K S Galpin ◽  
R G Henderson ◽  
W P T James ◽  
P Trayhurn
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cytochrome Oxidase ◽  
Oxidase Activity ◽  
Cytochrome Oxidase Activity ◽  
Acute Response ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis ◽  
Ad Libitum ◽  
Stimulation Of

Cytochrome oxidase activity and mitochondrial GDP binding were decreased in brown adipose tissue of mice treated chronically with corticosterone. These changes occurred both in corticosterone-treated mice fed ad libitum and in treated mice pair-fed to control animals. Although the dietary stimulation of brown-adipose-tissue thermogenesis was suppressed by corticosterone, the acute response to cold was not affected.

Inhibition by Oxytetracycline of the Development of the Enhanced Response to Noradrenaline in Cold-Acclimated Rats: A New Approach to the Study of Nonshivering Thermogenesis

1971 ◽  
Vol 49 (6) ◽  
pp. 545-553 ◽  
Author(s):  
Jean Himms–Hagen
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cytochrome Oxidase ◽  
Oxidase Activity ◽  
Metabolic Response ◽  
Inner Membrane ◽  
Cytochrome Oxidase Activity ◽  
Mitochondrial Inner Membrane ◽  
Brown Adipose

The aim of these experiments was to depress the increased metabolic activity of the brown adipose tissue in the intact rat during acclimation to cold in order to elucidate further the possible thermogenic and endocrine functions of this tissue. The antibiotic oxytetracycline was administered twice daily for 2 weeks to rats living at 4 °C in an attempt to inhibit the proliferation of mitochondria and of mitochondrial inner membrane known to occur in the brown adipose tissue in response to cold; control rats received saline during the same period. Total cytochrome oxidase activity served as an index of the amount of mitochondrial inner membrane in brown adipose tissue, liver, and skeletal muscle. The development of an enhanced calorigenic response to intravenously infused noradrenaline served as an index of the extent of acclimation to cold.Treatment with oxytetracycline inhibited both the cold-induced increase in cytochrome oxidase activity in brown adipose tissue and the cold-induced development of an enhanced calorigenic response to noradrenaline in the intact rats; a direct correlation was noted between the amount of cytochrome oxidase in brown adipose tissue and the size of the metabolic response to noradrenaline of the intact animals. However, the amount of oxygen that could be consumed by the total cytochrome oxidase in the brown adipose tissue was itself too small to account for the increase in oxygen consumption by the rat. Treatment of the rats with oxytetracycline did not alter the cold-induced growth of brown adipose tissue (as judged by the increase in wet weight and the increase in total protein); it also did not alter the cytochrome oxidase activities of liver or skeletal muscle. The effect of oxytetracycline seems, therefore, to be fairly specific for the mitochondria of the most rapidly dividing tissue, the brown adipose tissue. The conclusion is drawn that a protein synthesized in the mitochondria of the brown adipose tissue in response to cold is essential for adaptation to cold.

Evidence that fasting can induce a selective loss of uncoupling protein from brown adipose tissue mitochondria of mice

1986 ◽  
Vol 6 (9) ◽  
pp. 805-810 ◽  
Author(s):  
P. Trayhurn ◽  
G. Jennings
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cytochrome Oxidase ◽  
Oxidase Activity ◽  
Uncoupling Protein ◽  
Cytochrome Oxidase Activity ◽  
Selective Loss ◽  
Brown Adipose ◽  
Fasting And Refeeding ◽  
Total Tissue

The effects of fasting and refeeding on the concentration of uncoupling protein in brown adipose tissue mitochondria have been investigated in mice. Fasting mice for 48 h led to a large decrease in the total cytochrome oxidase activity of the interscapular brown fat pad. Mitochondrial GDP binding and the specific mitochondrial concentration of uncoupling protein also fell on fasting. After 24 h refeeding both GDP binding and the mitochondrial concentration of uncoupling protein were normalized, but there was no alteration in the total tissue cytochrome oxidase activity. Fasting appears to induce a selective loss of uncoupling protein from brown adipose tissue mitochondria, which is rapidly reversible on refeeding.

Effect of adrenalectomy and glucocorticoid replacement on development of obesity

1986 ◽  
Vol 250 (4) ◽  
pp. R595-R607 ◽  
Author(s):  
M. R. Freedman ◽  
B. A. Horwitz ◽  
J. S. Stern
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Protein Content ◽  
Body Fat ◽  
Plasma Insulin ◽  
Tissue Protein ◽  
Steroid Dose ◽  
Brown Adipose ◽  
Obese Rats

Female obese and lean Zucker rats were adrenalectomized (ADX) or sham-operated at 4 wk of age. ADX animals were given daily injections of 0.01, 0.05, 0.50, 1.0, or 2.0 mg hydrocortisone/100 g body wt for 30 days. ADX rats gained less weight than sham-operated controls. Obese ADX rats at the lowest dose (0.01) had a net positive energy gain but lost body fat. As steroid dose increased, obese rats deposited more fat and less protein. Doses of 0.01 and 0.05 mg produced rats that were less fat than sham-operated controls, whereas doses of 0.50, 1.0, and 2.0 mg produced rats of comparable body fat composition. Obese rats were consistently fatter and had a significantly smaller percentage body protein than lean rats at each dose. Body fat elevation was reflected by heavier parametrial and retroperitoneal fat depots and larger fat cells at all doses except the lowest. Compared with sham-operated controls, lean and obese rats at the two lowest replacement doses (0.01, 0.05) exhibited significantly decreased plasma insulin and triglyceride levels and significantly elevated brown adipose tissue protein content and citrate synthase (CS) activity. Obese rats at these doses had significantly reduced adipose tissue lipoprotein lipase (LPL) activity in the retroperitoneal depot and lower food intake. Furthermore, these obese rats had adipose depot weights, cell sizes, LPL activity, and plasma insulin, glucose, and triglyceride comparable to that of lean sham-operated controls. As steroid dose increased (0.5, 1.0, 2.0), plasma insulin and triglyceride and food intake markedly increased only in obese rats. Adipose tissue LPL activity appeared unaffected by dose. Brown adipose tissue protein content and CS activity significantly decreased as dose increased in both lean and obese rats. At all doses of replacement obese rats were more responsive to steroid than were lean rats. Obese rats receiving 0.01 mg had comparable fat depot weights, cell sizes, and plasma insulin and triglyceride as lean rats receiving 50 times as much steroid per day (0.50 mg). These results suggest glucocorticoids play an important role in the early development of obesity in the Zucker rat and support the hypothesis that obese rats are more responsive to glucocorticoids than are lean rats.

scholarly journals Brown Adipose Tissue: A New Target for Antiobesity Therapy

2010 ◽  
Vol 2 (2) ◽  
pp. 4
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Positive Energy ◽  
The Past ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Adult Humans ◽  
Thermogenic Capacity

BACKGROUND: Human fat consist of white and brown adipose tissue (WAT and BAT). Though most fat is energy-storing WAT, the thermogenic capacity of even small amounts of BAT makes it an attractive therapeutic target for inducing weight loss through energy expenditure.CONTENT: Over the past year, several independent research teams used a combination of positron-emission tomography and computed tomography (PET/CT) imaging, immunohistochemistry and gene and protein expression assays to prove conclusively that adult humans have functional BAT. BAT is important for thermogenesis and energy balance in small mammals and its induction in mice promotes energy expenditure, reduces adiposity and protects mice from diet-induced obesity. The thermogenic capacity of BAT is impressive. In humans, it has been estimated that as little as 50g of BAT could utilize up to 20% of basal caloric needs if maximally stimulated.SUMMARY: The obesity pandemic requires new and novel treatments. The past few years have witnessed multiple studies conclusively showing that adult humans have functional BAT, a tissue that has a tremendous capacity for obesity-reducing thermogenesis. Novel therapies targeting BAT thermogenesis may be available in the near future as therapeutic options for obesity and diabetes. Thermogenic ingredients may be considered as functional agents that could help in preventing a positive energy balance and obesity.KEYWORDS: brown adipose tissue, thermogenesis, energy expenditure, antiobesity therapy

Responses to cafeteria feeding in mice after the removal of interscapular brown adipose tissue

1982 ◽  
Vol 2 (11) ◽  
pp. 877-882 ◽  
Author(s):  
E. Connolly ◽  
J. A. Carnie
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Protein Content ◽  
Total Protein ◽  
Oxidase Activity ◽  
Total Protein Content ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Wet Weight

Feeding acafeteria diet to mice resulted in an increased energy intake of approximately 30% and this led to increases in the wet weight, total protein content, and total cytochrome oxidase activity of interscapular and dorso-cervical brown adipose tissue. Surgical removal of interscapular brown adipose tissue, followed by cafeteria feeding, gave rise to an elevation in dorso-cervical brown adipose tissue wet weight, total protein content, and total cytochrome oxidase activity, compared to intact cafeteria-fed mice. Cafeteria feeding with or without the removal of interscapular brown adipose tissue did not lead to significant increases in body weight compared to stock-fed control mice, but both cafeteria-fed groups of mice showed significant elevations in body fat content indicating that the induced hyperphagia led to a relative obesity in the cafeteria-fed groups. The results presented are consistent with an increased thermogenic activity in the brown adipose tissue of cafeteria-fed mice, and the effect of the removal of interscapular brown adipose tissue further indicates the quantitative importance of the tissue in the control of body weight.

Changes in cytochrome oxidase activity in brown adipose tissue during oestrous cycle in the rat

1998 ◽  
Vol 139 (4) ◽  
pp. 433-437 ◽  
Author(s):  
M Puerta ◽  
M Rocha ◽  
S Gonzalez-Covaleda ◽  
S. McBennett ◽  
J. Andrews
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cytochrome Oxidase ◽  
Oxidase Activity ◽  
Oestrous Cycle ◽  
Cytochrome Oxidase Activity ◽  
Brown Adipose
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