Catecholamine-stimulated Lipolysis Research Articles

Lack of beta 3-adrenergic effect on lipolysis in human subcutaneous adipose tissue.

Human adipocytes are responsive to both alpha- (antilipolytic) and beta-(lipolytic) actions of catecholamine agonists. These effects are mediated by G proteins which interact with adenylcyclase beta 1- and beta 2-adrenoreceptor (AR) subtypes are identified in human adipose tissue. The existence of a third beta-adrenergic (beta 3) receptor has been recently proposed. The beta 3-AR has been reported to mediate catecholamine-induced cAMP accumulation and to be more responsive in this regard than either the beta 1- or the beta 2-AR. To examine the possibility that a beta 3-AR plays a significant role in the control of catecholamine-stimulated lipolysis in human adipose tissue, we used a sensitive in vitro measure of lipolysis. Abdominal and gluteal sc adipose tissue samples from 14 adults were incubated with isoproterenol, a nonspecific beta-AR agonist which activates adenylyl cyclase via all three beta-AR subtypes, in the presence of varying concentrations of a beta-AR antagonist, alprenolol, which blocks the beta 1- and beta 2-AR, but not the beta 3-AR. In tissue from both abdominal and gluteal sites, alprenolol (10(-3) M) completely abolished the lipolytic response to isoproterenol (10(-6) M). Alprenolol (10(-3) M) alone reduced basal lipolysis by 10.2 +/- 2.2% (SEM) in abdominal tissue (P < 0.01), and 7.1 +/- 2.7% in gluteal tissue (P < 0.05). In the presence of alprenolol (10(-3) M), isoproterenol (10(-6) M) had no demonstrable lipolytic effect. The probability of incorrect acceptance of the null hypothesis that isoproterenol had no effect on lipolysis in alprenolol-blocked tissue is P beta < 0.05 for both depots. As an additional control, pooled inguinal adipose tissue from adult male Sprague-Dawley rats was incubated with the same concentrations of alprenolol. Rat adipose tissue has been previously shown to express the beta 3-adrenoreceptor and lipolysis was increased in rat adipose tissue in the presence of alprenolol 10(-4) M and 10(-5) M. We conclude that beta 3-ARs, if present in human adipocyte plasma membranes, do not significantly affect rates of lipolysis.

Modulation by sex hormones of the membranous transducing system regulating fatty acid mobilization in adipose tissue

This review summarizes recent animal studies performed to determine the possible role played by sex hormones in the sex- and site-related differences characterizing adipocyte lipolytic activity. In both normal female rats and male hamsters, fat cells from deep intra-abdominal sites elicit higher catecholamine-stimulated lipolytic responses than subcutaneous adipocytes. By using ovariectomized rats, it was found that estradiol ‘in vivo’, while having no effect in subcutaneous cells, promotes catecholamine-stimulated lipolysis in deep intra-abdominal adipocytes by increasing their adenylate cyclase catalytic activity. By using castrated hamsters, it was found that both deep intra-abdominal and subcutaneous fat cell lipolytic activities are equally sensitive to testosterone. In these cells, testosterone treatment promotes not only the β-adrenergic lipolytic responses by increasing both the adenylate cyclase catalytic activity and the Gsα level, but also enhances the α2-adrenergic antilipolytic responses through a transcriptional activation of the α2-adrenoceptor expression. These experiments demonstrate that in some, but not all, white adipocytes the adrenergic signal transducing system regulating lipolysis is a target for sex hormones. This finding may have potential importance in the understanding of the mechanisms underlying the sex-related regional specificities of adipose tissue metabolism and distribution.

Abnormalities of carbohydrate and lipid metabolism in Dahl rats.

Plasma glucose, insulin, and triglyceride concentration, blood pressure, and insulin action on isolated adipocytes were determined in weight-matched Sprague-Dawley, Dahl salt-resistant, and Dahl salt-sensitive rats. Blood pressure and plasma glucose concentrations were not significantly different in the three groups. However, Dahl salt-sensitive rats had significantly higher plasma insulin (39 +/- 2 microunits/ml) and triglyceride (213 +/- 11 mg/dl) concentrations than did Sprague-Dawley rats (27 +/- 2 microunits/ml and 101 +/- 6 mg/dl, respectively). Values for insulin (34 +/- 4 microunits/ml) and triglyceride (159 +/- 11 mg/dl) were intermediate in Dahl salt-resistant rats. In contrast, maximal insulin-stimulated glucose transport was significantly lower in adipocytes isolated from Dahl salt-sensitive as compared with Sprague-Dawley rats (400 +/- 16 versus 523 +/- 14 fl/cell/sec), with Dahl salt-resistant rats again having intermediate values. However, the ability of insulin to maximally inhibit catecholamine-stimulated lipolysis was similar in all three groups, averaging approximately 20% of the activity present in the absence of insulin. All of these differences were seen when the rats were eating conventional chow and did not change in Dahl rats after 2 weeks of an 8% NaCl diet. On the other hand, the predicted rise in blood pressure took place in Dahl salt-sensitive rats, increasing from 147 +/- 4 to 181 +/- 6 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic regulation of lipolysis in human fat cells during exercise

The adrenergic regulation of lipolysis was studied, before and after 30 min of submaximal exercise, in isolated adipocytes removed from the abdominal and gluteal regions of healthy non-obese men and women. Noradrenaline-induced lipolysis was significantly enhanced in gluteal adipocytes from men but not in women after exercise. However, the pure beta-adrenergic responsiveness was equally increased in gluteal adipocytes of both sexes after exercise, as judged by the effect of isoprenaline. Furthermore, the alpha 2-adrenergic anti-lipolytic responsiveness was more apparent after exercise in females than in males thereby counter-balancing the increase in the beta-adrenergic effect in the gluteal region in the former. The increased beta-adrenergic responsiveness induced by exercise in gluteal adipocytes of males could be mimicked by agents acting at the levels of adenylate cyclase, coupling proteins, phosphodiesterase, and protein kinase and seems to be due to an adaptive enhancement at the hormone-sensitive-lipase level. There was no change in the stoichiometric properties of beta-adrenoceptors of gluteal adipocytes after exercise. Abdominal adipocytes of both sexes were four to five times more responsive to noradrenaline than gluteal ones. However, exercise induced no further enhancement of the catecholamine-stimulated lipolysis rate in fat cells from this site. Thus, the influence of exercise on catecholamine-stimulated lipolysis is regional and sex dependent. Men, but not women, have a greater ability to adapt lipolysis to increasing energy demands during exercise that are due to an acute increase in the effectiveness of the hormone-sensitive lipase complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Catecholamine-induced lipolysis in adipose tissue of the elderly.

Age-dependent alterations in the effects of catecholamines on lipolysis were investigated in 25 young (21-35 yr) and 10 elderly (58-72 yr) healthy, nonobese subjects using isolated adipocytes obtained from abdominal subcutaneous tissue. Basal lipolysis was not affected by aging, while the rate of catecholamine-stimulated lipolysis was reduced by 50% in the elderly subjects (P less than 0.005). To elucidate the mechanisms behind this phenomenon lipolysis was stimulated with agents that act at well-defined steps in the lipolytic cascade, from the receptor down to the final step: the activation of the protein kinase/hormone-sensitive lipase complex. All agents stimulated lipolysis at a 50% lower rate in elderly as compared with young subjects (P less than 0.05 or less). However, half-maximum effective concentrations of the lipolytic agents were similar in both groups. The antilipolytic effects of alpha 2-adrenoceptor agonists were also the same in young and old subjects. Moreover, the stoichiometric properties of the beta- and alpha 2-receptors did not change with increasing age. In vivo studies performed on the same individuals likewise demonstrated an impaired lipolytic responsiveness, with 50% lower plasma glycerol concentrations during exercise in the elderly subjects (P less than 0.05), in spite of a normal rise in plasma norepinephrine. The plasma glycerol levels correlated strongly to the glycerol release caused by catecholamine-stimulated lipolysis in vitro in both young and elderly subjects (r = 0.8-0.9, P less than 0.001). In conclusion, a decreased activation of the hormone-sensitive lipase complex appears to be the mechanism underlying a blunted lipolytic response of fat cells to catecholamine stimulation in elderly subjects. This finding may, explain the age-dependent decreased lipolytic response to exercise in vivo.

D-(—)-β-hydroxybutyrate inhibits catecholamine-stimulated lipolysis and decreases β-adrenoceptors' affinity in human fat cells but not in lymphomonocytes

The effect of D-(-)-beta-hydroxybutyrate, at concentrations commonly achieved during ketoacidosis in humans (10 mmol/l), on human fat cell lipolysis in vitro was the aim of this study. The basal lipolysis was not modified and beta-hydroxybutyrate did not affect forskolin- or dibutyryl-cAMP-stimulated glycerol release, whereas it markedly inhibited isoproterenol-stimulated lipolysis. In membranes of intact adipocytes exposed to D-(-)-beta-hydroxybutyrate for 1 h, we found a decrease in beta-adrenoceptor affinity in saturation experiments and a shift to the right of the isoproterenol-mediated radioligand [( 125I]-cyanopindolol) displacement curve. These findings suggest that beta-hydroxybutyrate inhibits catecholamine-stimulated lipolysis by decreasing beta-adrenoceptor affinity. No effect of beta-hydroxybutyrate was found on beta-adrenoceptor binding of intact mononuclear cells of peripheral blood. In conclusion, the beta-adrenoceptor affinity lowering effect of beta-hydroxybutyrate is seemingly specific to human fat cells and might represent a feed-back mechanism that prevents an uncontrolled breakdown of triglycerides and indirectly regulates its own production rate.

Metabolism of adipose tissue in intraabdominal depots of nonobese men and women

Adipocyte size, lipoprotein lipase (LPL) activity, and the lipolytic response to noradrenaline and isoproterenol were studied in three intraabdominal depots (mesenteric, omental, retroperitoneal), as well as in subcutaneous abdominal adipose tissue, in nonobese groups of middle-aged men and in premenopausal and postmenopausal women. Subcutaneous adipocytes were larger than intraabdominal adipocytes in all groups. The men had large adipocytes in all intraabdominal depots as compared with the women. The premenopausal women seemed to have low LPL activity in intraabdominal depots. Two types of response to catecholamine-stimulated lipolysis were observed: a similar response from mesenteric and omental (portal) fat depots and from retroperitoneal and subcutaneous abdominal (nonportal) fat depots. Young women had higher lipolysis in nonportal than in portal adipose tissues. In the men the reverse characteristics were found. These dissimilarities seem to be based on differences in β-adrenergic responsiveness. Postmenopausal women showed no differences between depots. The differences in lipolytic responsiveness between these groups might be caused by sex steroid hormones.

Regulation of Bovine Adipose Tissue Metabolism During Lactation. 5. Relationships of Lipid Synthesis and Lipolysis with Energy Intake and Utilization1,2

The effects of energy utilization during lactation on adipose tissue metabolism were determined in 51 first lactation Holstein heifers producing between 5950 and 10,246kg milk in 305 d. Net energy intake ranged from 18.3 to 40.6 Mcal/d during 28 to 140 d of lactation. Milk yield ranged from 13.5 to 47.4 kg/d and fat percent from 1.49 to 4.60 during 28 to 140 d, providing a range of 8.2 to 32.6 Mcal/d milk energy secretion. Calculated energy balance ranged from −16.4 to 11.5 Mcal/d. Weight change ranged from −70 to 143kg during that 112-d period. Subcutaneous adipose tissue was biopsied nine times from 30 d prepartum to 15 d after lactation ceased. Adipose lipid synthesis measured prepartum was negatively related to subsequent milk energy secretion. Net energy intake, body weight, and body weight change were related positively to adipose lipid synthesis rates from 28 to 56 d, but those rates were related negatively to milk energy secretion. Lipolysis was positively related to milk energy secretion and body weight and negatively related to NE intake. At d 60 of lactation, adipose tissue lipid synthesis rates were a function of body weight, weight gain, and net energy intake. However, catecholamine-stimulated lipolysis rates were a function of body weight and milk energy secretion. After 140 d, lipid synthesis and lipolysis were elevated and more closely related to the previous peak rather than to concomitant milk energy secretion. These relationships demonstrate the effects of dietary energy content and genetic selection for milk production on adipose tissue metabolism.

Influence of a small molecular weight proteinase inhibitor, gabexate mesilate (FOY), on insulin receptor function in vitro.

The effects of the low molecular weight serine proteinase inhibitor FOY (gabexate mesilate) upon insulin action was studied in three different experimental systems. Placenta membranes containing insulin receptors preincubated with FOY (10 microM) showed a reduction of insulin-stimulated tyrosine kinase activity (p less than 0.01). However, FOY (0.1-100 microM) did not affect the insulin-stimulated tyrosine kinase activity in a preparation of solubilized and partially purified insulin receptors from placental membranes. Isolated adipocytes were used to study the effect of FOY on intact cells. FOY neither altered the insulin induced inhibition of the catecholamine-stimulated lipolysis nor (at the low concentration of 0.1 mM) the stimulation of glucose transport by the hormone. High concentrations (0.5 mM) of FOY decreased the effect of insulin on the hexose transport.

Phospho-dephospho-control by insulin is mimicked by a phospho-oligosaccharide in adipocytes.

The mechanism of insulin action is only partly understood. At one end of the signalling chain, the structure of the insulin receptor is known in detail, and at the other end, insulin controls cellular metabolism by regulating the phosphorylation of serine and threonine residues in key target enzymes. The molecular events linking the occupied receptor to changes in target enzyme phosphorylation have remained obscure. Recently, insulin was shown to promote the hydrolysis of a phosphatidylinositol glycan with release of its polar head-group. The head group was reported to activate a high-affinity cyclic AMP-phosphodiesterase and pyruvate dehydrogenase, to inhibit catecholamine-stimulated lipolysis, and also to inhibit phospholipid methyltransferase and adenylate cyclase. We report here that in intact adipocytes this head-group faithfully copies the insulin-directed effects on the phosphorylation and dephosphorylation of target proteins of the hormone.

Antilipolytic activity of viprostol, a transdermally active antihypertensive PGE 2 analog

Viprostol, a novel prostaglandin E 2 congener, was assessed for in vitro antilipolytic activity in the spontaneously obese rat. In isolated epididymal adipocytes, viprostal exhibited a dose-dependent inhibition of catecholamine-stimulated lipolysis at concentrations ranging from 10 μM to 1 mM, but was ineffective at lower concentrations. Additionally, viprostal exhibited approximately 50% of the antilipolytic activity of naturally-occurring PGE 1 and PGE 2 at similar concentrations, but was as potent as PGF 2α. At 10 μM, viprostol inhibited maximum catecholamine-stimulated lipolysis by approximately 35% of the total, hormone-stimulated glycerol release. The results of these experiments indicate that viprostol exhibits antilipolytic activity in vitro , but is less potent than the naturally-occurring PGE's to which it is most closely related structurally.

Adenosine regulates blood flow and glucose uptake in adipose tissue of dogs.

Intravenous norepinephrine increases glycerol release and blood flow in adipose tissue. The vasodilation may be an indirect effect of norepinephrine through the production of adenosine. Adenosine increases glucose uptake and inhibits lipolysis in vitro. To test whether adenosine regulates blood flow and/or metabolism in vivo, adenosine deaminase (ADA) was infused intra-arterially into the inguinal fat pads of anesthetized dogs. In unstimulated tissues, ADA (n = 7) significantly increased vascular resistance and significantly decreased glucose uptake compared with the effects of a control (boiled deaminase, n = 6) infusion. ADA completely blocked the norepinephrine-induced vasodilation (n = 6). No potentiation of basal or catecholamine-stimulated lipolysis was observed with ADA. The presence of ADA in the interstitial space was verified by analysis of lymph effluents. Interstitial levels of ADA were inversely correlated with the tissue contents of adenosine. These data support the hypothesis that adenosine is a regulator of blood flow in basal and stimulated adipose tissue. Adenosine also appears to regulate glucose uptake, but not lipolysis, in vivo.

Influence of a low molecular weight serine proteinase inhibitor (camostate) on lipolysis of isolated adipocytes.

The effect of the epsilon-guanidino acid derivate camostate (FOY 305) on lipolysis of isolated adipocytes was evaluated to test its supposed influence on the reactions of lipid metabolism in experimental shock. Isoprenaline (10(-6) M) and theophylline (10(-3) M) significantly stimulated lipolysis in vitro. The basal submaximal (isoprenaline 10(-6)-10(-9) M) and maximal (isoprenaline 10(-6) M) catecholamine-stimulated lipolysis were not affected by camostate (10(-6) M). Furthermore, camostate (0.1-100 X 10(-6) M) did not influence half-maximal theophylline-induced lipolysis of the adipocytes. Our findings do not support the suggestion that epsilon-guanidino acid derivatives diminish in shock the increase of free fatty acids in blood via an influence on lipolysis in the peripheral adipose tissue.

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 doseresponse 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.

The antilipolytic, insulin-like effect of growth hormone is caused by a net decrease of hormone-sensitive lipase phosphorylation.

The mechanism of the antilipolytic effect of GH and the cause of refractoriness to its own action was studied in isolated rat adipocytes. Human GH rapidly inhibited catecholamine-stimulated lipolysis rate, with a time course similar to that of insulin, but only in cells which had been preincubated in the absence of GH for 2-3 h. Half-maximal inhibition was obtained with a GH concentration of 100 ng/ml. Parallel determinations of the lipolysis rate (with a pH-stat titration technique) and the extent of phosphorylation of hormone-sensitive lipase, the rate-controlling enzyme in adipose tissue lipolysis, were made. The extent of lipase phosphorylation, 1.7-fold enhanced by previous noradrenaline stimulation, was rapidly reversed by addition of GH, and the decrease was followed by a parallel decrease in the lipolysis rate. The time course and magnitude of these effects was similar to those obtained with exposure of the cells to insulin, indicating that the antilipolytic effect of both hormones was exerted through the same mechanism: a net dephosphorylation of the hormone-sensitive lipase. To study the refractoriness of the fat cells to the action of GH (which was not found with insulin) adipocytes were prepared from hypophysectomized rats 24 h after surgery. With such cells no preincubation was required to obtain the effects of GH on the lipolysis rate and extent of hormone-sensitive lipase phosphorylation. The effects of GH on both of the parameters studied were similar to those obtained in nonhypophysectomized rats. These results suggest that the refractoriness of the fat cells to GH may be explained by a functional inhibition at a site(s) in the series of metabolic events initiated by GH action, which precedes the activation of the hormone-sensitive lipase.

Absence of α-adrenergic inhibition of lipolysis in swine adipose tissue

1. Adipose tissue slices from young and older pigs and genetically obese pigs were incubated to demonstrate α-adrenergic inhibition of lipolysis as found by other investigators in dog, guinea-pig, hamster, human and rabbit adipose tissue. 2. Purported α-adrenergic agonists (amidephrine, clonidine, methoxamine, phenylephrine) did not inhibit basal or catecholamine-stimulated lipolysis. 3. Purported α-adrenergic antagonists (dihydroergotamine, phenoxybenzamine, phentolamine, prazosin, yohimbine) did not enhance basal or stimulated lipolysis. 4. Adipose tissue from pigs is different from that of most species but similar to that of rats with no α-adrenergic inhibition of lipolysis.

Effect of locally released catecholamines on lipolysis and injury of the hypoxic isolated rabbit heart

The ability of endogenous myocardial catecholamines to stimulate lipolysis of endogenous triglycerides and the role of this process in the development of myocardial injury were studied in isolated, Langendorff-perfused rabbit heart preparations exposed to 3 h of hypoxic perfusion followed by 30 min of aerobic perfusion. Untreated hearts responded not only to hypoxia but also to reoxygenation with surges of noradrenaline outflow lasting 10 and 5 min, respectively. During hypoxia but not during reoxygenation a parallel surge of glycerol outflow was observed. Nicotinic acid (10 −5 m) prevented glycerol outflow during hypoxia but did not influence the outflow of noradrenaline during either hypoxia or reoxygenation. Neither noradrenaline nor glycerol were detected in the effluent from the hearts depleted of endogenous catecholamines by reserpine pretreatment. Those hearts also showed a smaller lactate dehydrogenase release during hypoxia (49% reduction) and no increase in lactate dehydrogenase release during reoxygenation. Similar reduction of lactate dehydrogenase release during hypoxia (52% reduction) was observed in the hearts treated with nicotinic acid. This drug, however, did not prevent the reoxygenation-induced lactate dehydrogenase release. The effects of reserpinization and nicotinic acid treatment on lactate dehydrogenase release were not additive. It is concluded that hypoxia is a stimulus for lipolysis in the isolated rabbit heart and most probably this process is catecholamine dependent. At least part of the deleterious effect of endogenous catecholmines on hypoxic myocardium might be attributed to catecholamine-stimulated lipolysis of endogenous triglycerides. The latter, however, does not seem to contribute to deleterious effects of endogenous catecholamines during reoxygenation.

Enhanced receptor-cyclase coupling and augmented catecholamine-stimulated lipolysis in exercising rats.

To test the hypothesis that alterations of adipocyte beta-adrenergic receptors provide a molecular mechanism for enhanced catecholamine-stimulated lipolysis in physically trained animals, we studied adipocytes derived from rats subjected to 14 wk of swimming and from sedentary controls. Peak glycerol release and peak adenylate cyclase activity in response to epinephrine were increased in swimmers to 255% (P less than 0.01) and 156% (P less than 0.01) of control values, respectively, but neither basal glycerol release, basal cyclase activity, NaF-stimulated cyclase activity, beta-receptor number, nor receptor affinity for [3H]dihydroalprenolol were altered. Epinephrine-stimulated adenylate cyclase activity remained increased in adipocytes from swimmers in the presence of theophylline or adenosine. In the absence of exogenous guanine nucleotide, we observed no differences in the dissociation constants for either the high-affinity (KD = 0.025 microM) or the low-affinity (KL = 11 microM) classes of binding sites for (-)-epinephrine, but the proportion of high-affinity sites was greater in membrane preparations from swimmers than from controls (74 vs. 42%; P less than 0.01). We conclude that receptor-cyclase coupling is enhanced in adipocytes from exercising rats, perhaps due to an improved ability of adrenergic agonists to form the guanine nucleotide reversible high-affinity agonist-receptor complex.

Analysis of apparent co-operativity in the catecholamine-stimulated lipolysis of rat adipose tissue

(1) The methods available for assessment of the regulatory features of dose-response relationships that do not conform to the Hill equation are considered, and the sensitisation index S i introduced. (2) The value of determining S i is assessed using lipolytic dose-response relationships yielded by β-adrenergic agonists both alone and in the presence of their specific antagonists [D. M. F. Cooper and J. I. Davies, Biochem. Pharmac. 31, 721 (1982)]. (3) It is shown that where the Hill equation is fitted to relationships between l-noradrenaline concentration and lipolysis, the high value obtained for the Hill coefficient (1.69) is artefactual. (4) By fitting a rational quadratic model and evaluating S i , a solution is obtained ( S i (max), 1.02) which is free of this artefact. (5) The relationship between the results obtained by analysis of dose-response curves and direct binding of catecholamine analogues to membrane receptors is discussed.

Effects of insulin on lipolysis and lipogenesis in hamster white adipocytes with high sensitivity to hormones

A modified procedure for preparation of hamster adipocytes by collagenase digestion under carefully controlled conditions has been developed. The adipocytes were 4- to 8-fold more sensitive to catecholamine stimulation of lipolysis than cells prepared by a commonly used method (Hittelman, K.J., Wu, C.F. and Butcher, R.W. (1973) Biochim. Biophys. Acta 304, 188–196) and also more sensitive to the anti-lipolytic action of insulin. The effects of insulin on lipogenesis, measured as [ 3H]glucose conversion to cell lipids, and on catecholamine-stimulated lipolysis were compared under identical conditions with the same cell batch. Isoprenaline-stimulated lipolysis was found to be half-maximally inhibited by an insulin concentration 8-fold lower than that stimulating lipogenesis to a corresponding extent (half-maximal effects at insulin concentrations of 40 vs. 300 pM). A similar difference was found when cells had been stimulated with adrenaline instead of isoprenaline.