The activation of the adipose tissue associated with lymph nodes during the early stages of an immune response

The effects of repeated local immune challenges with lipopolysaccharide (LPS) over 24 h on basal and noradrenaline-stimulated lipolysis and the development of sensitivity to interleukin-4 and tumour necrosis factor-alpha in adipocytes associated with lymph nodes were studied in adult guinea-pigs. Properties characteristic of perinodal adipocytes appeared in adipocytes at least 10 mm from the locally stimulated popliteal lymph node within 12 h, and in other node-containing depots over 24 h. All effects appeared first in perinodal adipocytes and spread as though in response to signals emanating from the enclosed lymph node. The popliteal depot was more completely activated than the mesenteric, but its maximum rate of lipolysis/100 adipocytes was lower. None of the pre-treatments in vivo, nor incubation with cytokines in vitro modulated lipolysis in adipocytes from the nodeless perirenal depot. The sensitivity of the perinodal adipocytes to cytokines changed within 3 h of immune stimulation, preceding detectable increases in lipolysis. Cytokine-stimulated and noradrenaline-stimulated lipolysis sum, suggesting separate pathways. We conclude that sustained local activation of a single popliteal lymph node recruits additional adipocytes in node-containing depots only. Signals spread from lymph nodes to surrounding adipocytes, but the time courses of activation of adipocytes and their maximum responses differ between the mesenteric and popliteal depots.     

Site-specific differences in the action of NRTI drugs on adipose tissue incubated in vitro with lymphoid cells,and their interaction with dietary lipids

Existing theories of the origin of HIV-related adipose tissue redistribution syndrome cannot adequately explain simultaneous hypertrophy of certain depots and atrophy of others, or its occasional occurrence in untreated HIV infection. These experiments explore the hypothesis that hypertrophy of lymphoid tissue-containing adipose depots arises from drug-induced disruption to local interactions between perinodal adipocytes and activated lymphoid cells. Guinea pigs were fed on plain or lipid-supplemented (10% suet, sunflower or fish oil) chow ad libitum or restricted, and the popliteal lymph nodes were activated by repeated injection of lipopolysaccharide. Explants of perinodal and other samples from popliteal, mesentery, omentum and nodeless perirenal and epididymal depots were incubated with lymphoid cells and zidovudine, didanosine, lamivudine or stavudine at physiological concentrations (0.1-1 microg/ml) or interleukin-10 and interleukin-6, and basal and maximum lipolysis was measured. All drugs increased lipolysis from perinodal adipocytes, especially mesenteric, though less than exogenous cytokines. Effects on adipocytes from non-perinodal sites and nodeless depots were minimal. The sunflower-oil diet enhanced, and the fish-oil and restricted diets reduced, these effects. We conclude that these NRTI antiretroviral drugs modulate the local interactions between perinodal adipocytes and activated lymphoid cells. Local interactions, and hence the selective hypertrophy of node-containing adipose depots, may be curtailed by dietary manipulation.     

Adipose tissue,the immune system and exercise fatigue: how activated lymphocytes compete for lipids

Adipose depots that contain lymph nodes, and probably intermuscular fat in skeletal and cardiac muscle, are specialized to provision adjacent tissue in a paracrine mode. Perinodal adipocytes respond selectively to various cytokines and incorporate proportionately more polyunsaturated fatty acids. Lipolysis in the adipocytes of node-containing depots can be stimulated via inflammation of the enclosed lymph nodes. Repeated immune stimulation elicits properties characteristic of perinodal adipocytes in those elsewhere in the same depot, and hours later in other node-containing depots, but not in nodeless depots. Such site-specific properties of adipose tissue enable partitioning of dietary and metabolic supplies of fatty acids between competing tissues. Local interactions emancipate the peripheral immune system from competing with other tissues for lipids during immune responses, and may be especially important during periods of high demand, such as strenuous exercise. Biopsies of subcutaneous adipose tissue from sites remote from lymph nodes do not adequately represent the composition of fatty acids available to the immune system in situ, and perhaps that supplied to other tissues. Intermuscular fat in skeletal and cardiac muscle may also indicate paracrine relationships between adipocytes and "end-user" tissues. The concept of paracrine interactions between certain adipocytes and "user" tissue may account for the widespread contiguity between these tissues in vivo.     

Changes in lymphokine receptor expression and fatty acid composition of phospholipids and triacylglycerols in rat adipocytes associated with lymph nodes following a transient immune challenge

Single-photon counting fluorimetry was used to record the time course of the expression of interleukin-10 receptors labelled with fluorescent antibodies on the surface of adipocytes over 24h, following an immune challenge to the rat popliteal lymph node. Homologous perinodal and remote-from-node samples from the stimulated and unstimulated popliteal depots were compared in rats fed on plain chow and chow supplemented with 10% w/w suet, fish or vegetable oils. Receptor expression was maximal 6 h after stimulation, and returned to baseline after 24 h, and was similar in the stimulated and unstimulated depots. Fewer receptors were elicited in tissues from rats fed lipid-supplemented diets compared with the control diet, with fewest of all following the fish oil diet. These data suggest that interleukin-10 is involved in local interactions between perinodal adipocytes and lymph node lymphoid cells. Both triacylglycerols and phospholipids contained more polyunsaturates and fewer saturates in perinodal adipose tissue than in samples from sites not associated with lymphoid tissue. These data are consistent with paracrine interactions between perinodal adipocytes and activated lymphoid cells.     

Adipose tissue and the immune system

Adipocytes anatomically associated with lymph nodes (and omental milky spots) have many special properties including fatty acid composition and the control of lipolysis that equip them to interact locally with lymphoid cells. Lymph node lymphocytes and tissue dendritic cells acquire their fatty acids from the contiguous adipocytes. Lymph node-derived dendritic cells suppress lipolysis in perinodal adipocytes but those that permeate the adipose tissue stimulate lipolysis, especially after minor, local immune stimulation. Inflammation alters the composition of fatty acids incorporated into dendritic cells, and that of node-containing adipose tissue, counteracting the effects of dietary lipids. Thus these specialised adipocytes partially emancipate the immune system from fluctuations in the abundance and composition of dietary lipids. Prolonged, low-level immune stimulation induces the local formation of more adipocytes, especially adjacent to the inflamed lymph node. This mechanism may contribute to hypertrophy of the mesentery and omentum in chronic inflammatory diseases such as HIV-infection, and in smokers. Paracrine interactions between adipose and lymphoid tissues are enhanced by diets rich in n-6 fatty acids and attentuated by fish oils. The latter improve immune function and body conformation in animals and people. The partitioning of adipose tissue in many depots, some specialised for local, paracrine interactions with other tissues, is a fundamental feature of mammals.     

Paracrine interactions of mammalian adipose tissue

Adipose tissue develops in and/or around most lymphoid tissues in mammals and birds. Early reports of this widespread association and hypotheses for its functional basis were long ignored in the planning of in vitro studies and the interpretation of in vivo results. Biochemical studies on rodent tissues reveal many site-specific properties of adipocytes anatomically associated with lymph nodes and omental milky spots that equip them to interact locally with lymphoid cells. The paracrine interactions are strongest for the most readily activated lymph nodes and are modulated by dietary lipids. Perinodal adipocytes contribute less than those in the large nodeless depots to whole-body lipid supplies during fasting. Observations on wild animals show that perinodal adipose tissue is selectively conserved even in starvation but does not enlarge greatly in natural obesity. Such paracrine provisioning of peripheral immune responses improves their efficiency and emancipates activated lymphocytes from competition with other tissues for blood-borne nutrients. The relationship is found in extant protherians and metatherians, so it almost certainly arose early in the evolution of mammals, possibly as part of the metabolic reorganisation associated with homeothermy, viviparity, and lactation. Prolonged disruption to paracrine interactions between lymphoid and adipose tissue may contribute to the HIV-associated adipose redistribution syndrome, causing selective hypertrophy of the mesentery, omentum, and other adipose depots that contain much activated lymphoid tissue. Skeletal and cardiac muscle may also have paracrine relationships with anatomically associated adipose tissue, but interactions between contiguous tissues have not been demonstrated directly.     

The effects of exercise and feeding on the activity of lipoprotein lipase in nine different adipose depots of guinea pigs.

1. The activity of lipoprotein lipase (LPL) was measured in whole adipose tissue from 9 identified adipose depots of sedentary, fasting adult guinea pigs and following 30 min of exercise or voluntary ingestion of chow, and in adipocyte and stromal-vascular fractions from exercised specimens. 2. In sedentary, fasting specimens, LPL activity was up to 4 times higher in the small intermuscular depots than in the perirenal and epididymal depot (Table 1). 3. LPL activity increased significantly after feeding only in the large superficial depot, groin, and in the perirenal depot. LPL activity decreased after exercise only in the 2 intermuscular depots and in small anterior superficial depots. These effects of exercise were consistently greater in males than in females (Table 3). 4. Following exercise, there was up to twice as much LPL in the adipocytes as in the stromal-vascular fraction of the intermuscular depots, about 50% more in adipocytes from the minor superficial depots and about equal quantities in the 2 fractions of the intra-abdominal and groin depots (Table 2). 5. The data demonstrate the physiological inhomogeneity of both superficial and internal adipose depots, and are consistent with the hypothesis that LPL originating from adipose tissue may enter the circulation.     

Incorporation of glucose into lipid of perirenal and subcutaneous adipocytes of rats and sheep: influence of insulin

Adipocytes were prepared by collagenase digestion of perirenal and subcutaneous fat from rats and sheep and were incubated in vitro with various concentrations of glucose and insulin. The lipogenic rate of perirenal and subcutaneous adipocytes of rats showed a quadratic response to glucose concentration. The addition of 10 nM insulin increased lipogenesis, especially at low lipogenic rates. At constant glucose concentrations, insulin concentrations up to 50 nM stimulated lipogenesis a similar amount in adipocytes from both depots. The rate of lipogenesis increased relative to cell volume in perirenal adipocytes only. The lipogenic rate of perirenal and subcutaneous adipocytes of sheep showed a positive linear response to glucose concentration, but insulin did not affect the rate of lipogenesis in adipocytes from either depot. In both rats and sheep, the rate of lipogenesis was higher in the perirenal adipocytes. It was concluded that insulin is unlikely to be the agent responsible for the differential growth rates of subcutaneous and perirenal fat depots in rats or sheep.     

Adipogenic and lipolytic effects of chronic glucocorticoid exposure

Glucocorticoids have been proposed to be both adipogenic and lipolytic in action within adipose tissue, although it is unknown whether these actions can occur simultaneously. Here we investigate both the in vitro and in vivo effects of corticosterone (Cort) on adipose tissue metabolism. Cort increased 3T3-L1 preadipocyte differentiation in a concentration-dependent manner, but did not increase lipogenesis in adipocytes. Cort increased lipolysis within adipocytes in a concentration-dependent manner (maximum effect at 1-10 μM). Surprisingly, removal of Cort further increased lipolytic rates (～320% above control, P < 0.05), indicating a residual effect on basal lipolysis. mRNA and protein expression of adipose triglyceride lipase and phosphorylated status of hormone sensitive lipase (Ser563/Ser660) were increased with 48 h of Cort treatment. To test these responses in vivo, Sprague-Dawley rats were subcutaneously implanted with wax pellets with/without Cort (300 mg). After 10 days, adipose depots were removed and cultured ex vivo. Both free fatty acids and glycerol concentrations were elevated in fed and fasting conditions in Cort-treated rats. Despite increased lipolysis, Cort rats had more visceral adiposity than sham rats (10.2 vs. 6.9 g/kg body wt, P < 0.05). Visceral adipocytes from Cort rats were smaller and more numerous than those in sham rats, suggesting that adipogenesis occurred through preadipocyte differentiation rather than adipocyte hypertrophy. Visceral, but not subcutaneous, adipocyte cultures from Cort-treated rats displayed a 1.5-fold increase in basal lipolytic rates compared with sham rats (P < 0.05). Taken together, our findings demonstrate that chronic glucocorticoid exposure stimulates both lipolysis and adipogenesis in visceral adipose tissue but favors adipogenesis primarily through preadipocyte differentiation.     

Sex- and depot-specific lipolysis regulation in human adipocytes: interplay between adrenergic stimulation and glucocorticoids

The purpose of this investigation was to explore interactions between adrenergic stimulation, glucocorticoids, and insulin on the lipolytic rate in isolated human adipocytes from subcutaneous and omental fat depots, and to address possible sex differences. Fat biopsies were obtained from 48 nondiabetic subjects undergoing elective abdominal surgery. Lipolysis rate was measured as glycerol release from isolated cells and proteins involved in lipolysis regulation were assessed by immunoblots. Fasting blood samples were obtained and metabolic and inflammatory variables were analyzed. In women, the rate of 8-bromo-cAMP- and isoprenaline-stimulated lipolysis was approximately 2- and 1.5-fold higher, respectively, in subcutaneous compared to omental adipocytes, whereas there was no difference between the two depots in men. Dexamethasone treatment increased the ability of 8-bromo-cAMP to stimulate lipolysis in the subcutaneous depot in women, but had no consistent effects in fat cells from men. Protein kinase A, Perilipin A, and hormone sensitive lipase content in adipocytes was not affected by adipose depot, sex, or glucocorticoid treatment. In conclusion, catecholamine and glucocorticoid regulation of lipolysis in isolated human adipocytes differs between adipose tissue depots and also between sexes. These findings may be of relevance for the interaction between endogenous stress hormones and adipose tissue function in visceral adiposity and the metabolic syndrome.     

Serum levels of interleukin 1beta, interleukin 8 and tumour necrosis factor alpha as markers of gastric cancer.

Despite the efforts made, a serum marker reliable for the screening and follow-up of patients with gastric cancer has not yet been identified. The aim of this preliminary study was to test the role of pro-inflammatory cytokines interleukin 1beta, interleukin 8 and tumour necrosis factor alpha in patients with gastric cancer and in control groups. The statistical analysis of cytokines serum levels in the group with gastric cancer versus control groups has shown considerable differences (p < 0.001) in their mean rates. The results indicate that the cytokines interleukin 1beta, interleukin 8 and tumour necrosis factor alpha might perhaps act as diagnostic markers in patients with gastric cancer. Therefore, it is hypothesized that after more extended trials, their use in the screening and prognostic assessment of these patients could be a possibility.     

Adipose tissue in the mammalian heart and pericardium: structure, foetal development and biochemical properties

1. The occurrence and relative abundance of adipose tissue around the heart and in the pericardium of wild and domesticated mammals are reviewed and some new data reported. 2. For macaque monkeys and a wide range of other adult mammals, the mean volume of epicardial adipocytes is constant at about half the average of that of other depots, although the relative mass of this depot is unrelated to the abundance of adipose tissue in the rest of the body. 3. In young adult guinea-pigs, the maximum rate of fatty acid synthesis is significantly higher in epicardial adipose tissue than that in the pericardial, perirenal and popliteal depots. 4. The rate of fatty acid release by epicardial adipose tissue is approximately twice that of the pericardial and perirenal depots. 5. The protein contents of guinea-pig epicardial and pericardial adipose tissue are similar, and are significantly higher than those of the perirenal and popliteal adipose tissue and there are no site-specific differences in the abundance of mitochondria. 6. In adult Macaca monkeys, the capacity of the epicardial adipose tissue for glucose utilization is about half that of the intra-abdominal depots. 7. The principal difference between epicardial adipose tissue and that elsewhere in the body is its greater capacity for fatty acid release. 8. It is suggested that cardiac adipose tissue may act as a local energy supply for adjacent myocardium and/or as a buffer against toxic levels of free fatty acids.     

Differential immune response of adipocytes to virulent and attenuated Mycobacterium tuberculosis

Mycobacterium tuberculosis (M. tb) takes advantage of various cell types, allowing it to remain in the host for long periods. Because adipocytes have been proposed as niches for dormant M. tb in the latent state, understanding the interaction of virulent M. tb with adipocytes is important. We compared changes in cytokine secretion from 3T3-L1 murine adipocytes infected with virulent M. tb H37Rv (V-M. tb) and attenuated M. tb H37Ra (A-M. tb) strains. Both strains maintained non-replicating states within adipocytes until 10 days post-infection. Adipocytes infected with V-M. tb secreted lower levels of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-12p40, IL-6, and IL-17, and lower levels of nitric oxide than those infected with A-M. tb. In contrast, the anti-inflammatory cytokines, IL-10 and IL-4, were markedly induced in V-M. tb-infected adipocytes versus those infected with A-M. tb at an early time point. Heat-killed or formalin-fixed bacteria induced lower levels of cytokines and no difference was observed between strains. Moreover, V-M. tb induced a high level of necrosis versus A-M. tb in conjunction with increased levels of LHD. These results suggest that V-M. tb regulates cytokine expression in its favor, increasing cytokines necessary for immune evasion and decreasing those required for protective immunity.     

Hormone-sensitive lipase-independent adipocyte lipolysis during beta-adrenergic stimulation, fasting, and dietary fat loading

In white adipose tissue, lipolysis can occur by hormone-sensitive lipase (HSL)-dependent or HSL-independent pathways. To study HSL-independent lipolysis, we placed HSL-deficient mice in conditions of increased fatty acid flux: beta-adrenergic stimulation, fasting, and dietary fat loading. Intraperitoneal administration of the beta(3)-adrenergic agonist CL-316243 caused a greater increase in nonesterified fatty acid level in controls (0.33 +/- 0.05 mmol/l) than in HSL(-/-) mice (0.12 +/- 0.01 mmol/l, P < 0.01). Similarly, in isolated adipocytes, lipolytic response to CL-316243 was greatly reduced in HSL(-/-) mice compared with controls. Fasting for 相似文献   

Regional and gender variations in adipose tissue lipolysis in response to weight loss.

Catecholamine-induced lipolysis was investigated in 32 obese subjects (14 men and 18 premenopausal women), aged 36-50 years, whose body mass index ranged from 30 to 42 kg/m(2). Isolated subcutaneous (subc) abdominal and femoral adipocytes were studied before and after a 15-week weight reducing program, during which mean body weight loss averaged 9 vs. 10 kg in women and men, respectively (P < 0.0001). Participants were re-examined when they were weight-stable. Fat cell weight decreased by about 15;-20% in both depots (P values ranging from 0.01 to 0.05). Epinephrine (mixed alpha2-/beta-adrenoceptor (AR) agonist) induced antilipolysis at low concentrations and a net lipolytic response at higher doses, irrespective of subjects' fatness and anatomic location of fat. Basal lipolysis, maximal lipolytic responses to isoprenaline (beta-AR agonist), dobutamine and procaterol (beta1- and beta2-AR agonists, respectively) as well as maximal antilipolytic effects of epinephrine or UK-14304 (alpha2-AR agonist) were similar before and after weight reduction. However, both beta- and beta2-AR lipolytic sensitivities and the beta-AR density were increased in both genders after weight reduction, this effect being more marked in subc abdominal than in femoral adipocytes (P values ranging from 0.001 to 0.05). The alpha2-AR antilipolytic sensitivity was reduced in adipose cells from both regions in women, but only in subc abdominal adipocytes in men (P < 0.05), although the alpha2-AR density remained unchanged after weight reduction. In conclusion, a moderate weight loss leads to a higher adipose cell lipolytic efficiency which is associated with changes at receptor levels (mainly an increased beta2- and a decreased alpha2-AR sensitivities), in both genders.     

Protective activity of the antilipopolysaccharide antibodies from human cord serum

We evaluated the ability of human maternal and cord serum antibodies to protect mice challenged with live Escherichia coli serotype O6:K2ac (E. coli O6). Mice received paired maternal or cord serum pools before a challenge with E. coli O6 to evaluate the mortality rate. All the pools were able to protect the animals challenged with bacteria except the test group from paired maternal and cord sera from preterm neonates containing less than 1.0 mg L(-1) immunoglobulin G antibody levels. In liver, spleen and mesenteric lymph nodes from the control group (phosphate-buffered saline), more than 10(2) CFU mL(-1) bacteria were found at 30 min and more than 10(5) CFU mL(-1) after 120 min. The test group showed lower bacterial counts in the organs, and no bacteria in the mesenteric lymph nodes during the evaluated period. Tumor necrosis factor alpha and interleukin 6 were undetectable in serum from animals pretreated with paired maternal and cord serum pools from full-term neonates and pools from preterm neonates containing high antibody and avidity levels. Our findings suggest that placental transfer of antilipopolysaccharide O6 immunoglobulin G antibodies to neonates has a high capacity to prevent lethal infection with E. coli O6 in a mouse protection model and that the degree of protection is determined by the concentration and avidity of these IgG antibodies.     

Regulation of lipolysis in isolated adipocytes of rainbow trout (Oncorhynchus mykiss): the role of insulin and glucagon

In the present study, we have examined the effects of insulin and glucagon on the lipolysis of rainbow trout (Oncorhynchus mykiss). To this end, adipocytes were isolated from mesenteric fat and incubated in the absence (basal lipolysis) or presence of different concentrations of insulin and glucagon. In addition, to further elucidate the effects of these hormones in vivo on adipocyte lipolysis, both fasting and intraperitoneal glucagon injection experiments were performed. Basal lipolysis, measured as the glycerol released in the adipocyte medium, increased proportionally with cell concentration and incubation time. Cell viability was verified by measuring the release of lactate dehydrogenase (LDH) activity in the medium. Insulin (at doses of 35 and 350 nM) decreased lipolysis in isolated adipocytes of rainbow trout in vitro, while glucagon was clearly lipolytic at concentrations of 10 and 100 nM. Furthermore, hypoinsulinemia induced by fasting, as well as glucagon injection, significantly increased lipolysis in isolated adipocytes approximately 1.5- and 1.4-fold, respectively, when compared with adipocytes from control fish. Our data demonstrate that lipolysis, as measured in isolated adipocytes of rainbow trout, can be regulated by both insulin and glucagon. These results not only indicate that insulin is an important hormone in lipid deposition via its anti-lipolytic effects on rainbow trout adipocytes, but also reveal glucagon as a lipolytic hormone, as shown by both in vitro and in vivo experiments.     

Limited effects of recombinant human and murine interleukin 1 and tumour necrosis factor on production of acute phase proteins by cultured rat hepatocytes

Albumin, fibrinogen, alpha 1-acid glycoprotein and cysteine proteinase inhibitor were determined by electroimmunoassay in the media of primary cultures of rat hepatocytes exposed to dialysed supernatants of rat, mouse and human macrophages or to recombinant human and murine interleukin 1 and tumour necrosis factor. Recombinant cytokines in the range of 1 to 1000 ng/ml caused only reduction of albumin synthesis and slight stimulation of alpha 1 acid glycoprotein production while crude preparations of macrophage cytokines elicited typical acute phase response. The results suggest that interleukin 1 or tumour necrosis factor are not likely the principal mediators responsible for the direct stimulation of normal rat hepatocytes to acute phase protein synthesis.     

Modulation of sulfur mustard induced cell death in human epidermal keratinocytes using IL-10 and TNF-alpha

We compared the effects of overexpressing a tightly regulated anti-inflammatory cytokine, interleukin 10 (IL-10), and the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) on sulfur mustard induced cytotoxicity in human epidermal keratinocytes. Both cytokines were overexpressed when compared with the cells transfected with the empty vector as determined by quantitative ELISA. Cells overexpressing interleukin 10 suppressed the pro-inflammatory cytokines interleukin 8 and interleukin 6 following exposure to 50-300 microM sulfur mustard. These cells exhibited delayed onset of sulfur mustard induced cell death. On the other hand, cells overexpressing tumor necrosis factor alpha induced a sustained elevation in both interleukin 6 and 8 expression following exposure to 50-300 microM sulfur mustard. These cells were sensitized to the effects of sulfur mustard that resulted in an increased sulfur mustard induced cell death. Normal human epidermal keratinocytes treated with sulfur mustard exhibited elevated levels of tumor necrosis factor alpha expression and increased activity of nuclear factor kappa B. Gene array data indicated that cells overexpressing interleukin 10 induced several genes that are involved in growth promotion and cell-fate determination. We, therefore, identify IL-10 and TNF-alpha signal transduction pathways and their components as possible candidates for early therapeutic intervention against sulfur mustard induced cell injury.     

Catecholamine-stimulated lipolysis in adipocytes of spontaneously hypertensive rats

We investigated the catecholamine-stimulated lipolytic response of perirenal adipocytes isolated from spontaneously hypertensive (SHR) and normotensive (C) rats of the Sprague-Dawley (SD) and Wistar-Kyoto (WKY) strain. Younger rats (10-17 weeks) were matched with respect to age and body weight. Age-matched SHR rats were smaller than their C counterparts, had equal-size adipocytes, and demonstrated lipolytic responses equal to C cells. Weight-matched SHR rats were older than normotensive controls, had larger adipocytes, and showed depressed norepinephrine (NE)-stimulated responses with a rightward shift in the dose-response curve. Rates of lipolysis of SHR and C cells were not different in the simultaneous presence of norepinephrine and theophylline. Nine- to ten-month-old rats were of comparable body weight and adipocyte size regardless of blood pressure status; however, SHR cells still showed a significantly blunted response to catecholamine stimulation. We conclude that (1) the NE-stimulated lipolytic response of adipocytes of SHR rats is significantly less than that elicited from C cells; (2) this function difference seems unrelated to a size difference between cells of younger, SHR and C rats, thus implicating the adrenergic system; and (3) whole body growth (as reflected by body weight) and perirenal adipocyte growth do not proceed in parallel in actively growing SHR rats.