Mechanisms of increased lipoprotein lipase in fat cells of obese Zucker rats

1991 ◽  
Vol 261 (5) ◽  
pp. E653-E660 ◽  
Author(s):  
S. K. Fried ◽  
I. J. Turkenkopf ◽  
I. J. Goldberg ◽  
M. H. Doolittle ◽  
T. G. Kirchgessner ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Lipoprotein Lipase ◽  
Bovine Milk ◽  
Zucker Rats ◽  
Fat Cells ◽  
Fat Cell ◽  
Cell Basis ◽  
Rat Adipocytes ◽  
Obese Rats ◽  
Obese Zucker Rats

The mechanisms underlying the increased activity of lipoprotein lipase (LPL) in adipocytes of genetically obese Zucker rats was studied. Relative rates of LPL synthesis (percent of total protein synthesis) determined by biosynthetic labeling and specific immunoprecipitation were similar in isolated fat cells from lean and obese rats, in the absence or presence of insulin. Insulin stimulated LPL synthesis as a result of a general increase in protein synthesis, and this effect was more marked in the obese fat cells. Levels of LPL mRNA, as a percent of total RNA, were also similar in fat cells from lean and obese rats. In contrast, when the data are calculated on a per fat cell basis, rates of LPL synthesis per fat cell are ninefold higher in obese compared with lean cells, accounting for the increase in LPL activity per fat cell. Fat cells from lean and obese rats showed similar rates of binding and degradation of purified bovine milk 125I-labeled LPL per unit fat cell surface area. Thus, on a per cell basis, rates of LPL turnover are increased in enlarged Zucker rat adipocytes, but there is no specific abnormality in the cellular regulation of LPL. Increases in LPL activity in obese rat adipocytes are related to an overall hyperresponsiveness to insulin effects on protein synthesis.

Adipose lipoprotein lipase in insulin-treated diabetic lean and obese Zucker rats

1982 ◽  
Vol 242 (6) ◽  
pp. E445-E450 ◽  
Author(s):  
C. P. Chan ◽  
J. S. Stern
Keyword(s):  
Cell Size ◽  
Lipoprotein Lipase ◽  
Genetic Factors ◽  
Diabetic Rats ◽  
Zucker Rats ◽  
Fat Pad ◽  
Fat Cell ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Highly Correlated

Obese and lean alloxan-diabetic rats were given daily injections of insulin for 9 days. Plasma glucose and insulin concentrations were not different between the two genotypes given comparable amounts of insulin. Carcass fat and epididymal and retroperitoneal fat pad weights increased as the dose of insulin was increased. At each of four doses, fatties had larger fat cells, bigger pads, and more body fat than lean rats. Adipose lipoprotein lipase (LPL) activity per pad or per fat cell was increased by insulin. Except for the lowest dose of insulin, LPL activity was higher in obese rats than in lean rats. LPL activity per cell and cell size were highly correlated. However, when differences in cell size were corrected for, no significant effect of genotype existed. Cardiac LPL activities were different between the two genotypes only in nondiabetic rats. These results suggested that both insulin and some other genetic factors were important in elevating adipose LPL activities and thus fat deposition in obese Zucker rats.

Effect of swim training on development of obesity in the genetically obese rat

1982 ◽  
Vol 242 (3) ◽  
pp. R204-R211 ◽  
Author(s):  
J. L. Walberg ◽  
P. A. Mole ◽  
J. S. Stern
Keyword(s):  
Body Composition ◽  
Food Restriction ◽  
Plasma Insulin ◽  
Cell Number ◽  
Skeletal Growth ◽  
Zucker Rats ◽  
Fat Cell ◽  
Full Development ◽  
Obese Rats ◽  
Obese Zucker Rats

Seven-week-old female lean and obese Zucker rats were swim trained or kept sedentary for 8 wk. Another group of obese rats was exercised plus food restricted. During exercise training, obese and lean rats ate more but gained less body weight than sedentary controls. Exercise favorably altered body composition, adipose cellularity, and plasma insulin of the obese rat. Exercise plus food restriction more dramatically affected body composition and adipose cellularity but was no more effective in depressing hyperinsulinemia than exercise alone. Following 8 wk of retirement, dorsal fat cell number remained depressed to formerly exercised obese rats whereas adipose cellularity in other depots, body composition, and plasma insulin were similar to control levels. Thus, exercise delayed but did not prevent the full development of obesity in the Zucker rat. Food restriction along with exercise resulted in more permanent effects on adipose cellularity than exercise alone but stunted muscle and skeletal growth.

scholarly journals Active involvement of PKC for insulin-mediated rates of muscle protein synthesis in Zucker rats

2004 ◽  
Vol 286 (5) ◽  
pp. E753-E758 ◽  
Author(s):  
James D. Fluckey ◽  
Ronald N. Cortright ◽  
Edward Tapscott ◽  
Timothy Koves ◽  
Latasha Smith ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Translation ◽  
Zucker Rats ◽  
Insulin Signal Transduction ◽  
Active Involvement ◽  
Obese Rats ◽  
Gf 109203X ◽  
Obese Zucker Rats

A recent report from our group demonstrated that insulin facilitates muscle protein synthesis in obese Zucker rats. The purpose of this study was to determine whether PKC, a probable modulator of insulin signal transduction and/or mRNA translation, has a role in this insulin-mediated anabolic response. In the first portion of the study, gastrocnemius muscles of lean and obese Zucker rats ( n = 5–7 for each phenotype) were bilaterally perfused with or without insulin to assess cytosolic and membrane PKC activity. Limbs perfused with insulin demonstrated greater PKC activity in both lean and obese Zucker rats ( P < 0.05) compared with no insulin, but overall activity was greater in obese animals (by ∼27% compared with lean, P < 0.05). To determine whether PKC plays a role in muscle protein synthesis, hindlimbs ( n = 6–8 for each phenotype) were bilaterally perfused with or without insulin and/or GF-109203X (GF; a PKC inhibitor). The presence of GF did not influence the rates of insulin-mediated protein synthesis in gastrocnemius muscle of lean Zucker rats. However, when obese rats were perfused with GF ( P < 0.05), the effect of insulin on elevating rates of protein synthesis was not observed. We also used phorbol 12-myristate 13-acetate (TPA, a PKC activator; n = 5–7 for each phenotype) with and without insulin to determine the effect of PKC activation on muscle protein synthesis. TPA alone did not elevate muscle protein synthesis in lean or obese rats. However, TPA plus insulin resulted in elevated rates of protein synthesis in both phenotypes that were similar to rates of insulin alone of obese rats. These results suggest that PKC is a modulator and is necessary, but not sufficient, for insulin-mediated protein anabolic responses in skeletal muscle.

Insulin stimulation of muscle protein synthesis in obese Zucker rats is not via a rapamycin-sensitive pathway

2000 ◽  
Vol 279 (1) ◽  
pp. E182-E187 ◽  
Author(s):  
James D. Fluckey ◽  
Steven C. Pohnert ◽  
S. Greg Boyd ◽  
Ronald N. Cortright ◽  
Todd A. Trappe ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Glucose Disposal ◽  
Zucker Rats ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Inhibitor Of Protein Synthesis ◽  
White Gastrocnemius ◽  
Stimulation Of

The obese Zucker rat is resistant to insulin for glucose disposal, but it is unknown whether this insulin resistance is accompanied by alterations of insulin-mediated muscle protein synthesis. We examined rates of muscle protein synthesis either with or without insulin in lean and obese Zucker rats with the use of a bilateral hindlimb preparation. Additional experiments examined insulin's effect on protein synthesis with or without rapamycin, an inhibitor of protein synthesis. Protein synthesis in red and white gastrocnemius was stimulated by insulin compared with control (no insulin) in obese ( n = 10, P < 0.05) but not in lean ( n = 10, P > 0.05) Zucker rats. In white gastrocnemius, rapamycin significantly reduced rates of protein synthesis compared with control in lean ( n = 6) and obese ( n = 6) rats; however, in red gastrocnemius, the attenuating effect of rapamycin occurred only in obese rats. The addition of insulin to rapamycin resulted in rates of synthesis that were similar to those for rapamycin alone for lean rats and to those for insulin alone (augmented) for obese rats in both tissues. Our results demonstrate that insulin enhances protein synthesis in muscle that is otherwise characterized as insulin resistant. Furthermore, rapamycin inhibits protein synthesis in muscle of obese Zucker rats; however, stimulation of protein synthesis by insulin is not via a rapamycin-sensitive pathway.

Association of fat cell size and paracrine growth factors in development of hyperplastic obesity

1998 ◽  
Vol 275 (6) ◽  
pp. R1898-R1908 ◽  
Author(s):  
Brenda G. Marques ◽  
Dorothy B. Hausman ◽  
Roy J. Martin
Keyword(s):  
Adipose Tissue ◽  
Growth Factors ◽  
Conditioned Medium ◽  
Cellular Proliferation ◽  
Cell Number ◽  
Zucker Rats ◽  
Fat Cell ◽  
Obese Rats ◽  
Paracrine Growth Factors ◽  
Obese Zucker Rats

Inguinal, epididymal, and retroperitoneal adipose tissue from lean and obese Zucker rats, 3–15 wk of age, was used to determine the association among adipocyte size distribution, the presence of paracrine growth factors in adipose tissue, and subsequent changes in adipocyte number. For each specific depot and time point, obese rats had a greater percentage of large adipocytes than did lean rats. A positive correlation ( P < 0.02) was found in obese rats between the percentage of inguinal and epididymal adipocytes in the 140- to 180-μm size range and the ability of conditioned medium prepared from these depots to stimulate cellular proliferation in a bioassay system utilizing preadipocytes from inguinal fat pads of normal rats. Proliferative activity of the conditioned medium from all depots in obese rats was positively correlated ( P < 0.01) to subsequent changes in fat cell number. The data presented here for the inguinal and epididymal depot of obese Zucker rats are consistent with the hypothesis that enlarged adipocytes secrete growth factors that induce preadipocyte proliferation.

Lipoprotein lipase activity and lipolysis after swim training in obese Zucker rats

1983 ◽  
Vol 245 (5) ◽  
pp. R706-R712
Author(s):  
J. L. Walberg ◽  
M. R. Greenwood ◽  
J. S. Stern
Keyword(s):  
Exercise Training ◽  
Lipoprotein Lipase ◽  
Food Restriction ◽  
Plasma Insulin ◽  
Zucker Rats ◽  
Lipoprotein Lipase Activity ◽  
Adipocyte Size ◽  
Metabolic Disturbances ◽  
Obese Rats ◽  
Obese Zucker Rats

Obese and lean Zucker rats, 7 wk old, were swim trained or kept sedentary. Another group of obese rats was food restricted and exercised. Half the rats were killed after training for 8 wk, the remainder were retired and killed after an additional 8 wk. Neither treatment decreased adipocyte size in obese rats. Although basal lipolysis per cell was elevated in obese rats, their adipocytes were insensitive to epinephrine at 15 and 23 wk of age. Exercise training did not affect lipolysis. At all ages, adipose lipoprotein lipase (LPL) capacity was higher in obese relative to lean rats. In obese rats, swim training and exercise plus food restriction increased adipose and gastrocnemius LPL activity and depressed plasma insulin and triglyceride levels. All effects of exercise were transient. Thus, exercise training improved some of the metabolic disturbances in the Zucker obese rat but did not normalize adipocyte size, LPL activity, or lipolysis.

Physical training of lean and genetically obese Zucker rats: effect on fat cell metabolism

1982 ◽  
Vol 243 (5) ◽  
pp. E418-E426 ◽  
Author(s):  
L. J. Wardzala ◽  
M. Crettaz ◽  
E. D. Horton ◽  
B. Jeanrenaud ◽  
E. S. Horton
Keyword(s):  
Glucose Metabolism ◽  
Glucose Transport ◽  
Cell Metabolism ◽  
Insulin Binding ◽  
Zucker Rats ◽  
Fat Cell ◽  
Obese Rats ◽  
Increased Sensitivity ◽  
Obese Zucker Rats ◽  
Adipose Cells

The effects of 6-wk treadmill training program on the metabolism of isolated adipose cells from obese (fa/fa) and lean (Fa/?) Zucker rats were studied. Glucose metabolism and transport, insulin binding, and lipolysis were measured in adipose cells prepared from sedentary control and exercise-trained (ET) lean and/or obese rats. Two- to threefold increases in glucose metabolism were observed in cells from lean and obese ET rats compared with their respective controls. However, the insulin concentrations giving half-maximal stimulation (measuring insulin sensitivity) did not change (approximately 8 microunits/ml in lean and approximately 45 microunits/ml in obese rats). In lean ET rats, glucose transport and maximal glucose metabolic capacity (transport not rate-limiting) were increased twofold and sensitivity of lipolysis to epinephrine was increased three- to fourfold. These were not measured in obese rats. The results suggest that training of both lean and obese Zucker rats increases glucose utilization in adipose cells by increasing both glucose transport and intracellular glucose metabolism. Increased triglyceride turnover is also suggested by the increased sensitivity of lipolysis to epinephrine.

scholarly journals High Na intake increases renal angiotensin II levels and reduces expression of the ACE2-AT2R-MasR axis in obese Zucker rats

2012 ◽  
Vol 303 (3) ◽  
pp. F412-F419 ◽  
Author(s):  
Preethi Samuel ◽  
Quaisar Ali ◽  
Rifat Sabuhi ◽  
Yonnie Wu ◽  
Tahir Hussain
Keyword(s):  
Sodium Intake ◽  
Zucker Rats ◽  
Kidney Cortex ◽  
Complex Nature ◽  
Ang Ii ◽  
Pronounced Increase ◽  
High Sodium ◽  
High Sodium Intake ◽  
Obese Rats ◽  
Obese Zucker Rats

High sodium intake is known to regulate the renal renin-angiotensin system (RAS) and is a risk factor for the pathogenesis of obesity-related hypertension. The complex nature of the RAS reveals that its various components may have opposing effects on natriuresis and blood pressure regulation. We hypothesized that high sodium intake differentially regulates and shifts a balance between opposing components of the renal RAS, namely, angiotensin-converting enzyme (ACE)-ANG II-type 1 ANG II receptor (AT1R) vs. AT2-ACE2-angiotensinogen (Ang) (1–7)-Mas receptor (MasR), in obesity. In the present study, we evaluated protein and/or mRNA expression of angiotensinogen, renin, AT1A/BR, ACE, AT2R, ACE2, and MasR in the kidney cortex following 2 wk of a 8% high-sodium (HS) diet in lean and obese Zucker rats. The expression data showed that the relative expression pattern of ACE and AT1BR increased, renin decreased, and ACE2, AT2R, and MasR remained unaltered in HS-fed lean rats. On the other hand, HS intake in obese rats caused an increase in the cortical expression of ACE, a decrease in ACE2, AT2R, and MasR, and no changes in renin and AT1R. The cortical levels of ANG II increased by threefold in obese rats on HS compared with obese rats on normal salt (NS), which was not different than in lean rats. The HS intake elevated mean arterial pressure in obese rats (27 mmHg) more than in lean rats (16 mmHg). This study suggests that HS intake causes a pronounced increase in ANG II levels and a reduction in the expression of the ACE2-AT2R-MasR axis in the kidney cortex of obese rats. We conclude that such changes may lead to the potentially unopposed function of AT1R, with its various cellular and physiological roles, including the contribution to the pathogenesis of obesity-related hypertension.

scholarly journals Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats

2005 ◽  
Vol 153 (6) ◽  
pp. 963-969 ◽  
Author(s):  
Dorte X Gram ◽  
Anker J Hansen ◽  
Michael Wilken ◽  
Torben Elm ◽  
Ove Svendsen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Sensory Nerve ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Nerve Activity ◽  
Calcitonin Gene ◽  
Obese Rats ◽  
Obese Zucker Rats

Objective: It has earlier been demonstrated that capsaicin-induced desensitization improves insulin sensitivity in normal rats. However, whether increased capsaicin-sensitive nerve activity precedes the onset of insulin resistance in diet-induced obesity – and therefore might be involved in the pathophysiology – is not known. Further, it is of relevance to investigate whether capsaicin desensitization improves glycaemic control even in obese individuals and we therefore chose the obese Zucker rats to test this. Design and methods: Plasma levels of calcitonin gene-related peptide (CGRP; a marker of sensory nerve activity) was assessed in 8-week-old Zucker rats. To investigate whether capsaicin desensitization (100 mg/kg at 9 weeks of age) would also ameliorate glycaemia in this non-diabetic model, we assessed oral glucose tolerance at 7 weeks after capsaicin. Results: It was found that plasma CGRP levels were elevated in obese Zucker rats prior to the onset of obesity (16.1±3.4 pmol/l in pre-obese Zucker rats vs 6.9±1.1 pmol/l in lean littermates; P = 0.015) despite similar body weights. Furthermore, capsaicin desensitization reduced both fasting blood glucose (4.3±0.2 mmol/l vs 5.1±0.2 mmol/l in controls; P = 0.050) as well as the mean blood glucose level during an oral glucose tolerance test (OGTT) (6.8±0.3 mmol/l vs 8.6±0.5 mmol/l in control obese rats; P = 0.024) whereas the plasma insulin levels during the OGTT were unchanged. However this did not lead to an improvement in insulin resistance or to a reduction of tissue triglyceride accumulation in muscle or liver. Conclusion: We concluded that capsaicin-induced sensory nerve desensitization improves glucose tolerance in Zucker rats. Since, in this study, plasma CGRP levels, a marker of sensory nerve activity, were increased in the pre-obese rats, our data support the hypothesis that increased activity of sensory nerves precedes the development of obesity and insulin resistance in Zucker rats.

scholarly journals Adipose-tissue-specific increase in glyceraldehyde-3-phosphate dehydrogenase activity and mRNA amounts in suckling pre-obese Zucker rats. Effect of weaning

1988 ◽  
Vol 254 (2) ◽  
pp. 483-487 ◽  
Author(s):  
I Dugail ◽  
A Quignard-Boulange ◽  
R Bazin ◽  
X Le Liepvre ◽  
M Lavau
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Zucker Rats ◽  
Tissue Specific ◽  
Gapdh Gene ◽  
Gapdh Activity ◽  
Weanling Rats ◽  
Obese Rats ◽  
Specific Increase ◽  
Obese Zucker Rats

The regulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression was studied during the onset of obesity in the genetically obese (fa/fa) rat by determination of GAPDH activity and hybridizable mRNA amounts in adipose tissue and liver from suckling and weanling rats. GADPH activity remained low throughout the suckling period, and a burst of activity occurred after weaning in both lean and obese pups. As early as 7 days of age, adipose tissue from pre-obese rats displayed a significant increase in enzyme activity, whereas no difference could be detected in the liver. In both suckling (16 days of age) and weanling (30 days of age) obese rats a proportionate increase in GAPDH activity and mRNA amounts was observed in adipose tissue, but not in liver. It is concluded that the obese genotype influences GAPDH gene expression at a pretranslational level and in a tissue-specific manner. This phenomenon could partly contribute to the hyperactive fat accretion in the obese rat, since glycolysis is the major metabolic pathway for lipogenic substrates in adipose tissue.

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