Obese Rabbits Research Articles

C14 Reduced response of isolated papillary muscles to isoproterenol in obese rabbits

C14 Reduced response of isolated papillary muscles to isoproterenol in obese rabbits

Obese hypertensive rabbits develop concentric and eccentric hypertrophy and diastolic filling abnormalities

We have developed a new small animal model of obesity in which rabbits fed a high fat diet develop abnormalities in common with obese humans, including left ventricular (LV) hypertrophy. Using M-mode and two dimensional Doppler echocardiography we examined the characteristics of LV hypertrophy and diastolic function in obese and lean rabbits. Obese rabbits had greater interventricular septum and LV posterior wall thicknesses and greater LV internal end-diastolic and end-systolic diameters. Functionally, obese rabbits had higher A/E ratios. Similarly to obese humans, obese hypertensive rabbits develop combined concentric and eccentric LV hypertrophy and diastolic filling abnormalities. Therefore, this model may be valuable in the study of the development and pathology of obesity-related LV hypertrophy.

Hypertension, cardiac hypertrophy, and neurohumoral activity in a new animal model of obesity.

Although obesity is a major risk factor for morbidity and mortality, the mechanisms mediating cardiovascular abnormalities in response to weight gain are unclear. One reason for the paucity of information in this area is the lack of appropriate animal models for the study of human obesity. Therefore, the goal of the present study was to develop a small animal model of dietary-induced obesity that mimics many of the characteristics of human obesity. We studied female New Zealand White rabbits fed either a normal (n = 17) or high-fat diet (n = 15) and examined the cardiovascular consequences of obesity, including changes in blood pressure, humoral activation, and end-organ effects such as cardiac hypertrophy. After 12 wk, rabbits on the high-fat diet were 46% heavier than their lean counterparts (5.49 +/- 0.09 vs. 3.77 +/- 0.06 kg, respectively; P = 0.0001). Obese rabbits had higher resting heart rates than lean rabbits (220 +/- 7 vs. 177 +/- 6 beats/min; P = 0.0001) and developed hypertension (96 +/- 2 vs. 85 +/- 1 mmHg; P = 0.0001), hyperinsulinemia (32.5 +/- 3.4 vs. 15.5 +/- 1.0 microU/ml; P = 0.0001), hyperglycemia (162.4 +/- 2.9 vs. 141.9 +/- 2.7 mg/dl; P = 0.0001), and elevated triglycerides (102.3 +/- 9.1 vs. 48.5 +/- 4.0 mg/dl; P = 0.0001). Obese rabbits also developed cardiac hypertrophy, as evidenced by left ventricular (LV) dry weights that were 52% greater in obese than in lean rabbits (P = 0.0003). In addition, LV total protein was increased in proportion to the increase in LV weight. The results of this study suggest that rabbits fed a high-fat diet for a period of 12 wk develop many of the characteristics of human obesity. The obese rabbit should provide a small and relatively inexpensive animal model to investigate mechanisms of obesity-related cardiovascular abnormalities.

Obese hypertensive rabbits develop concentric and eccentric hypertrophy and diastolic filling abnormalities

Obese hypertensive rabbits develop concentric and eccentric hypertrophy and diastolic filling abnormalities

Intramyocardial arterial cushions of coronary vessels in animals and humans: morphology, occurrence and relation to heart disease.

The existence of coronary endoarterial cushions (CEC) in the human heart as nonpathological, functional entities has been debated, and CEC have been sparsely reported in animals. Arterial cushions are localized thickenings that protrude into the lumen of specific arteries. We have identified CEC in the rhesus monkey, dog, sheep, goat, pig, rabbit and rat, and in the human heart. Two distinct types are described: the ovoid CEC arranged singly, in pairs, or in groups of three to four, and the less common polypoid CEC seen primarily in humans. The highest incidence of CEC in rabbits and humans was in the left ventricle in arteries 150-488 microns in diameter. Light and electron microscopy demonstrated intimal location with smooth muscle cells surrounded by ground substance, collagen and elastin fibers in a highly organized pattern. Nerve fibers identified by their immunoreactivity with antiserum to the vasodilatory calcitonin-gene-related peptide contacted the CEC along the tunica media and were occasionally seen within CEC. Arrangement and histological composition of CEC suggest a role in the regulation of local blood flow and myocardial perfusion. In human hearts, the CEC density index correlated highly with the degree of heart disease. In subjects with high heart disease rating, increased connective tissue, lipid-like infiltration and calcification was seen within CEC, and foam cells were present in CEC of obese rabbits. This suggests that CEC in coronary arteries could be predisposed sites of atherosclerosis, and that injured CEC can cause coronary artery spasm and ischemia. We conclude that CEC occur in animals and humans as innervated intimal smooth muscle cushions that might have a role in myocardial perfusion and heart disease.

Hemodynamic Alterations in Hypertensive Obese Rabbits

There is little information on changes in overall and regional hemodynamics in obesity-associated hypertension. Therefore, the purpose of this study was to determine alterations in overall and regional blood flows and resistances in adipose and nonadipose tissues in a new model of obesity-associated hypertension in rabbits. Sixteen female New Zealand White rabbits were fed either a maintenance or high-fat diet; after 8 to 12 weeks cardiac output and regional blood flows were measured with the use of radioactive microspheres. Obese rabbits (5.22 +/- 0.14 versus 3.66 +/- 0.04 kg) had higher blood pressure (113 +/- 3 versus 95 +/- 1 mm Hg), cardiac output (812 +/- 59 versus 593 +/- 47 mL/min), and heart rate (269 +/- 12 versus 219 +/- 9 beats per minute) and lower overall peripheral resistance (0.14 +/- 0.01 versus 0.17 +/- 0.01 mm Hg/[mL/min]) than lean rabbits. Compared with lean controls, obese rabbits had higher weights of the ventricles, kidneys, liver, ovaries, adrenals, diaphragm, and spleen. Absolute blood flows were greater in the ventricles, kidneys, lungs, and ovaries, but differences were minimized when flows were normalized for organ weight. Adipose tissue flow per gram weight was significantly lower and resistance higher in obese rabbits. However, calculated total adipose tissue flow was higher in obese rabbits (86 versus 45 mL/min). Absolute resistances were lower in the left ventricle, kidneys, and large intestine, but when resistances were indexed for organ weight, kidney resistance tended to be higher in obese rabbits. These results indicate that even short periods of obesity-associated hypertension result in marked overall and regional hemodynamic changes.

Processing of the lipid-mobilizing peptide β-lipotropin in rabbit adipose tissue

β-Lipotropin, a pituitary peptide, is a strong stimulator of lipolysis in rabbit adipose tissue. This polypeptide is shown to be degraded by intact fat pads, homogenized adipose tissue and adipocytes of the rabbit dependent on the amount of adipose tissue, time and the pH of the incubation medium. In subcellular fractions of rabbit adipocytes the proteolytic activity could be localized into the cytosol and the microsomal fraction. To obtain information about the processing of β-lipotropin in its target cell lipolysis and degradation of this polypeptide were investigated in the presence of inhibitors of distinct cellular mechanisms and in different physiological states such as obesity and starvation. Thus, the stronger lipolytic response in adipocytes from obese rabbits respectively animals fed ad libitum was accompanied by a significantly increased degradation in comparison to lean respectively starved rabbits. The six lysosomotropic agents (chloroquine, NH 4Cl, propranolol, quinacrine, acridine orange and tetracaine), the proteinase inhibitors α 2-macroglobulin and monodansylcadaverine, cellular ATP depletion by 2-deoxy- d-glucose and 2,4-dmitrophenol and the omission of Ca 2+ ions from the incubation medium inhibited dose-dependently the lipolytic activity as well as the degradation of β-lipotropin in intact and homogenized adipose tissue. Inhibitors of the cytoskeleton such as colchicine, cytochalasin B, vinblastine and concanavalin A also reduced lipolysis but only the degradation in intact adipose tissue. It can be concluded that after receptor-mediated uptake the cytoskeleton and lysosomal proteases are involved in the processing of β-lipotropin.

Increased lipolytic responsiveness to β-lipotropin in fat cells from obese rabbits

Journal Article Increased lipolytic responsiveness to β-lipotropin in fat cells from obese rabbits Get access W O Richter, W O Richter Medizinische Klinik, Klinikum Grosshadern, Universität München Search for other works by this author on: Oxford Academic Google Scholar B Jacob, B Jacob Medizinische Klinik, Klinikum Grosshadern, Universität München Search for other works by this author on: Oxford Academic Google Scholar P Schwandt P Schwandt Medizinische Klinik, Klinikum Grosshadern, Universität München Search for other works by this author on: Oxford Academic Google Scholar Acta Endocrinologica (Norway), Volume 110, Issue 1_Supplement_a, Apr 1979, Page S41, https://doi.org/10.1530/acta.0.109S041 Published: 01 April 1985

AN EXTRA-ADRENAL ACTION OF ADRENOCORTICOTROPHIN: PHYSIOLOGICAL INDUCTION OF LIPOLYSIS BY SECRETION OF ADRENOCORTICOTROPHIN IN OBESE RABBITS

The effect of minor stressful stimuli (saline infusions or venepunctures) on lipid mobilization (estimated by plasma free fatty acids (FFA) and glycerol levels) was studied in two strains of conscious rabbits of various ages. Infusions of 0.9% (w/v) NaCl solution induced a prompt increase of FFA levels in naturally obese rabbits while this effect was absent in younger lighter animals. Administration of propranolol (a beta-adrenoceptor blocking drug) beforehand did not prevent lipid mobilization. Adipose tissue in vitro was completely unresponsive to the lipid mobilizing action of adrenaline. The initial output of ACTH induced by stressful stimuli was quickly followed by the increase in the plasma concentration of FFA. A highly significant correlation (r = 0.84 or 0.85; P less than 0.01) existed between plasma ACTH and FFA levels 30 and 60 min after the start of stress. Dexamethasone completely prevented lipid mobilization while adipose tissue in vivo and in vitro responded strongly to ACTH. Consequently the lack of response of plasma FFA concentrations in corticosteroid-treated rabbits seemed to be linked to the failure of the pituitary gland to mobilize ACTH rather than to the unresponsiveness of adipose tissue to the pituitary hormone. Our data indicate that in the rabbit, under conditions of stress, ACTH is of greater physiological importance than catecholamines in the control of lipolysis.

LETHAL EFFECTS OF CORTICOTROPIN IN OBESE RABBITS.

LETHAL EFFECTS OF CORTICOTROPIN IN OBESE RABBITS.