White Adipose Tissue Lipoprotein Lipase Research Articles

6-OR: PAR2 Downregulates Adipose LPL through MIF—A Novel Adipose Mechanism Contributing to the Development of Hypertriglyceridemia

Lipoprotein lipase (LPL) is a key enzyme that hydrolyzes circulating triglycerides to release fatty acid (FA). In adipose tissue, LPL is required for lipid storage. However, it is currently unknown whether alteration of LPL in white adipose tissue (WAT) contributes to the development of hypertriglyceridemia. Our present study indicated that WAT isolated from human obese patients have increased expression of PAR2 which is negatively associated with LPL gene. The reduced LPL expression is also negatively correlated with increased plasma TG levels, suggesting that adipose PAR2 may modulate hyperlipidemia through downregulating LPL. In mice, aging and high palmitic oil diet significantly increased PAR2 expression in adipose tissue which was associated with high plasma MIF levels. PAR2 deficiency attenuates the rise of MIF, suggesting a key role of PAR2 in regulating adipose MIF release. MIF reduced LPL expression and activity in adipocytes. In a MIF overexpressed animal model (Mif lung Tg), high circulating MIF levels inhibited adipose LPL which was associated with increased plasma triglyceride but not fatty acid. Following high palmitic oil diet feeding, adipose LPL expression and activity were also reduced, and this reduction was reversed in PAR2 knockout mice. Interestingly, PAR2 mediated LPL in adipose tissue regulates hypertriglyceridemia through controlling adipocyte lipid storage. In Par2-/- mice, recombinant MIF perfusion recovered high plasma MIF levels, which decreased LPL and attenuated adipocyte lipid storage leading to hypertriglyceridemia. These data together suggest that the downregulation of adipose LPL by PAR2/MIF is an important mechanism for the development of hypertriglyceridemia. Disclosure Y.Huang: None. L.Li: None. L.Chen: None. X.Chen: None. P.Gao: None. Y.Qi: None. D.Qi: None. Funding Canadian Institutes of Health Research (PJT156116)

Role of Corticosterone in Lipid Metabolism in Broiler Chick White Adipose Tissue.

Excessive accumulation of body fat in broiler chickens has become a serious problem in the poultry industry. However, the molecular mechanism of triglyceride accumulation in chicken white adipose tissue (WAT) has not been elucidated. In the present study, we investigated the physiological importance of the catabolic hormone corticosterone, the major glucocorticoid in chickens, in the regulation of chicken WAT lipid metabolism. We first examined the effects of fasting on the mRNA levels of lipid metabolism-related genes associated with WAT, plasma corticosterone, and non-esterified fatty acid (NEFA). We then examined the effects of corticosterone on the expression of these genes in vivo and in vitro. In 10-day-old chicks, 3 h of fasting significantly decreased mRNA levels of lipoprotein lipase (LPL) in WAT and significantly elevated plasma concentrations of NEFA. Six hours of fasting significantly increased mRNA levels of adipose triglyceride lipase (ATGL) in WAT and significantly elevated plasma concentrations of corticosterone. On the other hand, fasting significantly reduced mRNA levels of LPL in WAT and elevated plasma concentrations of NEFA in 29-day-old chicks without affecting mRNA levels of ATGL in WAT or plasma corticosterone concentrations. Oral administration of corticosterone significantly reduced mRNA levels of LPL and significantly increased the mRNA levels of ATGL in WAT in 29-day-old chicks without affecting plasma NEFA concentrations. The addition of corticosterone to primary chicken adipocytes significantly increased mRNA levels of ATGL, whereas mRNA levels of LPL tended to decrease. NEFA concentrations in the culture medium were not influenced by corticosterone levels. These results suggest that plasma corticosterone partly regulates the gene expression of lipid metabolism-related genes in chicken WAT and this regulation is different from the acute elevation of plasma NEFA due to short-term fasting.

Mutation yellow in agouti loci prevents age-related increase of skeletal muscle genes regulating free fatty acids oxidation

The lethal yellow mutation in agouti loci (Ay mutation) reduces the activity of melanocortin (MC) receptors and causes hyperphagia, obesity and type two diabetes mellitus in aging mice (Ay mice). It is unknown if changes in distinct elements of the metabolic system such as white adipose tissue (WAT) and brown adipose tissue (BAT), and skeletal muscle will manifest before the development of obesity. The aim of this work was to measure the relative gene expression of key proteins that regulate carbohydrate-lipid metabolism in WAT, BAT and skeletal muscle in Ay mice before the development of obesity. C57Bl/6J mice bearing a dominant autosomal mutation Ay (Ay /a mice) and mice of the standard genotype (a/a mice, control) have been studied in three age groups: 10, 15 and 30 weeks. The relative mRNA level of genes was measured by real-time PCR in skeletal muscles (uncoupling protein 3 (Ucp3) and carnitine palmitoyl transferase 1b (Cpt1b) (free fatty acids oxidation), solute carrier family 2 (facilitated glucose transporter), member 4 (Slc2a4) (glucose uptake)), in WAT lipoprotein lipase (Lpl) (triglyceride deposition), hormone-sensitive lipase (Lipe) (lipid mobilization), and Slc2a4 (glucose uptake)), and in BAT: uncoupling protein 1 (Ucp1) (energy expenditure). The expression of Cpt1b was reduced in young Ay mice (10 weeks), there was no transient peak of transcription of Cpt1b, Ucp3 in skeletal muscle tissue and Lipe, Slc2a4 in WAT in early adult Ay mice (15 weeks), which was noted in а/а mice. Reduction of the transcriptional activity of the studied genes in skeletal muscle and white adipose tissue can initiate the development of melanocortin obesity in Ay mice.

Human hepatic lipase overexpression in mice induces hepatic steatosis and obesity through promoting hepatic lipogenesis and white adipose tissue lipolysis and fatty acid uptake.

Human hepatic lipase (hHL) is mainly localized on the hepatocyte cell surface where it hydrolyzes lipids from remnant lipoproteins and high density lipoproteins and promotes their hepatic selective uptake. Furthermore, hepatic lipase (HL) is closely associated with obesity in multiple studies. Therefore, HL may play a key role on lipid homeostasis in liver and white adipose tissue (WAT). In the present study, we aimed to evaluate the effects of hHL expression on hepatic and white adipose triglyceride metabolism in vivo. Experiments were carried out in hHL transgenic and wild-type mice fed a Western-type diet. Triglyceride metabolism studies included β-oxidation and de novo lipogenesis in liver and WAT, hepatic triglyceride secretion, and adipose lipoprotein lipase (LPL)-mediated free fatty acid (FFA) lipolysis and influx. The expression of hHL promoted hepatic triglyceride accumulation and de novo lipogenesis without affecting triglyceride secretion, and this was associated with an upregulation of Srebf1 as well as the main genes controlling the synthesis of fatty acids. Transgenic mice also exhibited more adiposity and an increased LPL-mediated FFA influx into the WAT without affecting glucose tolerance. Our results demonstrate that hHL promoted hepatic steatosis in mice mainly by upregulating de novo lipogenesis. HL also upregulated WAT LPL and promoted triglyceride-rich lipoprotein hydrolysis and adipose FFA uptake. These data support the important role of hHL in regulating hepatic lipid homeostasis and confirm the broad cardiometabolic role of HL.

A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase.

Lipasin/Angptl8 is a feeding-induced hepatokine that regulates triglyceride (TAG) metabolism; its therapeutical potential, mechanism of action, and relation to the lipoprotein lipase (LPL), however, remain elusive. We generated five monoclonal lipasin antibodies, among which one lowered the serum TAG level when injected into mice, and the epitope was determined to be EIQVEE. Lipasin-deficient mice exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white adipose tissue (WAT), suggesting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles. Consistently, mice injected with the effective antibody or with lipasin deficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state. These results suggest that lipasin acts, at least in part, in an endocrine manner. We propose the following model: feeding induces lipasin, activating the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating TAG to WAT for storage; conversely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skeletal muscles for oxidation. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses.

Thermogenic effect of triiodothyroacetic acid at low doses in rat adipose tissue without adverse side effects in the thyroid axis

Triiodothyroacetic acid (TRIAC) is a physiological product of triiodothyronine (T(3)) metabolism, with high affinity for T(3) nuclear receptors. Its interest stems from its potential thermogenic effects. Thus this work aimed 1) to clarify these thermogenic effects mediated by TRIAC vs. T(3) in vivo and 2) to determine whether they occurred predominantly in adipose tissues. To examine this, control rats were infused with equimolar T(3) or TRIAC doses (0.8 or 4 nmolx100 g body wt(-1) x day(-1)) or exposed for 48 h to cold. Both T(3) doses and only the highest TRIAC dose inhibited plasma and pituitary thyroid-stimulating hormone (TSH) and thyroxine (T(4)) in plasma and tissues. Interestingly, the lower TRIAC dose marginally inhibited plasma T(4). T(3) infusion increased plasma and tissue T(3) in a tissue-specific manner. The highest TRIAC dose increased TRIAC concentrations in plasma and tissues, decreasing plasma T(3). TRIAC concentrations in tissues were <10% those of T(3). Under cold exposure or high T(3) doses, TRIAC increased only in white adipose tissue (WAT). Remarkably, only the lower TRIAC dose activated thermogenesis, inducing ectopic uncoupling protein (UCP)-1 expression in WAT and maximal increases in UCP-1, UCP-2, and lipoprotein lipase (LPL) expression in brown adipose tissue (BAT), inhibiting UCP-2 in muscle and LPL in WAT. TRIAC, T(3), and cold exposure inhibited leptin secretion and mRNA in WAT. In summary, TRIAC, at low doses, induces thermogenic effects in adipose tissues without concomitant inhibition of TSH or hypothyroxinemia, suggesting a specific role regulating energy balance. This selective effect of TRIAC in adipose tissues might be considered a potential tool to increase energy metabolism.

Nitric Oxide and the Release of Lipoprotein Lipase from White Adipose Tissue

Background/Aim: Lipoprotein lipase (LPL) is the main enzyme responsible for the distribution of circulating triacylglycerides in tissues. Its regulation via release from active sites in the vascular endothelium is poorly understood. In a previous study we reported that in response to acute immobilization (IMMO), LPL activity rapidly increases in plasma and decreases in white adipose tissue (WAT) in rats. In other stress situations IMMO triggers a generalized increase in nitric oxide (NO) production. Methods/Results: Here we demonstrate that in rats: 1) in vivo acute IMMO rapidly increases NO concentrations in plasma 2) during acute IMMO the WAT probably produces NO via the endothelial isoform of nitric oxide synthase (eNOS) from vessels, and 3) epididymal WAT perfused in situ with an NO donor rapidly releases LPL from the endothelium. Conclusion: We propose the following chain of events: stress stimulus / rapid increase of NO production in WAT (by eNOS) / release of LPL from the endothelium in WAT vessels. This chain of events could be a new mechanism that promotes the rapid decrease of WAT LPL activity in response to a physiological stimulus.

Retroperitoneal white adipose tissue lipoprotein lipase activity is rapidly down-regulated in response to acute stress

Tissue-specific regulation of LPL has been widely studied in rats. Previous studies reported that in vivo administration of adrenaline and acute stress cause an increase in plasma LPL activity coinciding with a decrease in white adipose tissue (WAT) LPL activity. We studied the speed of LPL activity changes during 30 min of stress by immobilization (IMMO) in rats. A first experimental approach in permanently cannulated rats permitted sequential blood sampling in the same animal during IMMO and the obtaining of hemodynamic parameters. In a second experimental approach, animals were euthanized at different times after the start of IMMO to determine LPL activity in tissues. Stress was characterized by rises in blood pressure, heart rate, plasma corticosterone, and available circulating energy substrates. Five min after the start of IMMO, LPL activity fell in retroperitoneal WAT and increased in plasma. These data show the quickest LPL activity change ever described in response to a physiological situation. The speed and simultaneity of these changes suggest that the release from endothelium to the bloodstream may constitute a fast nonexplored mechanism of tissue LPL activity regulation, involved in the lipid energy-substrate redistribution between tissues needed to prepare the "fight-or-flight" response.

Bezafibrate improves bacterial lipopolysaccharide-induced dyslipidemia and anorexia in rats

Bacterial endotoxin/lipopolysaccharide (LPS)-induced cachexia is characterized by weight loss, anorexia, and a disturbance in lipid metabolism, namely, hypertriacylglycerolemia. The aim of this study in rats with acute endotoxicity induced by an injection of LPS was to investigate whether bezafibrate, a ligand for peroxisome proliferator–activated receptor α and a lipoprotein lipase (LPL) activator, improved cachectic conditions, including impaired lipid metabolism. Short-term administration of LPS in the rats resulted in impairment of triacylglycerol clearance in plasma after the intake of fresh cream. In addition, LPS increased whole-body energy expenditure, reduced fasting body weight and caused anorexia in the rats. Bezafibrate treatment resulted in significant improvements in LPS-induced dyslipidemia and anorexia, but had no effect on energy expenditure, respiratory quotient, or fasting body weight in the endotoxic rats. Administration of LPS was also associated with a decrease in the level of messenger RNA (mRNA) expression for LPL in white adipose tissue and skeletal muscle and an increase in the mRNA levels for uncoupling protein 3 in skeletal muscle. Bezafibrate treatment reversed the decline in LPL mRNA levels in white adipose tissue but not in the skeletal muscle tissue of the rats. The enhanced uncoupling protein 3 mRNA level in the endotoxic rats was not affected by bezafibrate treatment. Plasma concentration of leptin was increased by short-term LPS treatment. Bezafibrate decreased the level of plasma leptin significantly without affecting the level of leptin mRNA expression. These results suggest that bezafibrate may be an effective drug not only for impaired triacylglycerol metabolism, but also for anorexia in cachectic states induced by bacterial infections.

Transthyretin knockouts are a new mouse model for increased neuropeptide Y

Transthyretin (TTR) has access to the brain and nerve through the blood and cerebrospinal fluid. To investigate TTR function in nervous system homeostasis, differential gene expression in wild-type (WT) and TTR knockout (KO) mice was assessed. Peptidylglycine alpha-amidating monooxygenase (PAM), the rate-limiting enzyme in neuropeptide maturation, is overexpressed in the peripheral (PNS) and central nervous system (CNS) of TTR KOs that, consequently, display increased neuropeptide Y (NPY) levels. NPY acts on energy homeostasis by increasing white adipose tissue lipoprotein lipase (LPL) and decreasing thermogenesis; accordingly, we show increased LPL expression and activity in white adipose tissue, PNS, and CNS as well as decreased body temperature in TTR KOs. Associated to increased NPY levels, TTR KOs display increased carbohydrate consumption and preference. In neuronal cells, absence of TTR is related to increased PAM activity, NPY levels and LPL expression, reinforcing that TTR is involved in neuropeptide maturation and that increased NPY correlates with LPL overexpression in the nervous system. Furthermore, we provide molecular insights to the reduced depressive behavior of TTR KOs, as NPY is anti-depressant. Our findings demonstrate that TTR KOs are a model for increased NPY and that TTR plays a role in nervous system physiology.

Effect of oral oleoyl-estrone treatment on plasma lipoproteins and tissue lipase activities of Zucker lean and obese female rats.

To study the effect of oral oleoyl-estrone on the plasma lipoprotein profile and tissue lipase activities in order to determine the handling of circulating lipids by adipose tissue, liver and muscle of obese female rats. Lean (Fa/?) and obese (fa/fa) female Zucker rats treated for 10 days with a daily gavage of 0.2 ml sunflower oil containing 0 (controls) or 10 micromol/kg of oleoyl-estrone. After sacrifice, samples of tissues and plasma were taken. Plasma lipoprotein classes and composition; lipoprotein lipase and hepatic lipase activities in plasma, liver, skeletal muscle and periovaric and mesenteric white adipose tissue (WAT). Oleoyl-estrone decreased plasma cholesterol (mainly in HDLs: 76%) of lean rats, but dramatically decreased all lipid classes in obese rats, in which chylomicra and VLDL lost most of their triacylglycerols (95 and 81%, respectively). Hepatic lipase activity decreased markedly with oleoyl-estrone in all groups, both in plasma (79% lean, 100% obese) and liver (62% in both groups). Lipoprotein lipase activity was largely unchanged by oleoyl-estrone in lean rats, but in the obese it decreased in WAT (82% in periovaric, and 49% in mesenteric), and increased in plasma (x4) and in skeletal muscle (x5); liver levels showed no change. The shift observed in obese rats from a decrease in liver and WAT lipoprotein lipase and hepatic lipase activities to an increase in muscle lipoprotein lipase is coincident with the hypolipemic effect of oleoyl-estrone, especially in obese rats, and indicates that muscle is a key site for the disposal of endogenous fat mobilized due to oleoyl-estrone treatment.

Activation of PPARδ alters lipid metabolism in db/db mice

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which heterodimerize with the retinoid X receptor and bind to peroxisome proliferator response elements in the promoters of regulated genes. Despite the wealth of information available on the function of PPARα and PPARγ, relatively little is known about the most widely expressed PPAR subtype, PPARδ. Here we show that treatment of insulin resistant db/db mice with the PPARδ agonist L-165 041, at doses that had no effect on either glucose or triglycerides, raised total plasma cholesterol concentrations. The increased cholesterol was primarily associated with high density lipoprotein (HDL) particles, as shown by fast protein liquid chromatography analysis. These data were corroborated by the chemical analysis of the lipoproteins isolated by ultracentrifugation, demonstrating that treatment with L-165 041 produced an increase in circulating HDL without major changes in very low or low density lipoproteins. White adipose tissue lipoprotein lipase activity was reduced following treatment with the PPARδ ligand, but was increased by a PPARγ agonist. These data suggest both that PPARδ is involved in the regulation of cholesterol metabolism in db/db mice and that PPARδ ligands could potentially have therapeutic value.

Anti-Tumour Necrosis Factor-α Treatment Interferes with Changes in Lipid Metabolism in a Tumour Cachexia Model

1. Rats bearing the Yoshida ascites hepatoma AH-130 showed an important decrease in white adipose tissue lipoprotein lipase activity as compared with non-tumour bearing rats. This was associated with a lower adipose tissue mass, as estimated from the weight of the lumbar fat-pads. Conversely, lipoprotein lipase activity was markedly increased in brown adipose tissue and heart. 2. These changes were associated with a distinct hyperlipaemia, essentially manifested as an increase in circulating triacylglycerol levels, whereas no changes were observed in glycaemia. 3. Tumour-bearing rats were treated with a polyclonal anti-murine tumour necrosis factor-alpha antibody or with a non-immune IgG preparation. Control animals were either untreated or received a non-immune IgG preparation. Anti-tumour necrosis factor-alpha treatment resulted in a significant increase in lipoprotein lipase activity in white adipose tissue in animals bearing a tumour growing exponentially (day 4 after inoculation) as compared with the animals receiving a non-immune goat IgG preparation. In addition, animals bearing an stationary tumour (day 7 after inoculation) and submitted to anti-tumour necrosis factor-alpha treatment had a higher adipose tissue lipoprotein lipase activity as compared with the IgG- or the non-treated groups. Correspondingly, circulating triacylglycerol levels were markedly decreased, with a lower hyperlipaemia than in control tumour-bearing rats. 4. These observations suggest that tumour necrosis factor-alpha is involved in activating the lipid metabolic changes that develop in rats after transplantation of a fast-growing tumour.

A Pharmacodynamic Model of Triglyceride Transport and Deposition during Feed Deprivation or Following Treatment with 2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) in the Rat

A simplified model of fat metabolism was developed to predict fat synthesis, transport, deposition, and metabolism as a function of feed consumption, as a means of testing mechanisms proposed for the disruption in fat metabolism caused by TCDD. Rates of triglyceride (TG) synthesis and lipolysis were made directly dependent on daily average levels of feed consumption, which could be constant or follow other patterns. Seven compartments, including plasma very low density lipoprotein (VLDL) (1), plasma free fatty acid (FFA) (2), plasma VLDL remnants (3), lipoprotein lipase (LPL)-VLDL complex (4), liver TG (5), white adipose tissue (WAT) TG (6), and brown adipose tissue (BAT) TG (7) were required to obtain realistic rates of TG deposition in storage fat while maintaining normal levels of plasma TGs and FFA. The steady-state level of hepatic TG was very sensitive to the rate of storage fat lipolysis and hepatic VLDL export. Because plasma TG is taken up very rapidly by extra-hepatic tissues, reduction of WAT uptake rates had a greater effect on plasma TG than increasing rates of hepatic synthesis and VLDL export. Our results indicate that neither increased hepatic VLDL synthesis nor a simple inhibition of WAT LPL can, by themselves, explain the combined occurrence of hyperlipidemia and loss of fat observed in TCDDtreated animals. However, a TCDD-mediated enhancement of WAT TG lipolysis and consequential physiological responses in liver and BAT yield results compatible with experimental data.

Serum free fatty acids are not involved in acute exercise-induced reduction of LPL in rat tissues.

The present studies were designed to verify whether preventing the rise in serum levels of nonesterified fatty acids (NEFA) by adrenergic blockade would interfere with the decrease in tissue lipoprotein lipase (LPL) activity caused by acute exercise in rats. Ninety minutes before being killed, male rats were injected intraperitoneally with either saline, the beta-adrenergic blocker propranolol (25 mg/kg body weight), or the alpha 2-adrenergic blocker yohimbine (3 mg/kg body weight). Half of each group was killed at rest and the other half immediately after a 1-h run on a treadmill. LPL was determined in white adipose tissue (WAT), heart, and red vastus lateralis muscle (VLM). Exercise enhanced serum levels of NEFA 50% over resting values in saline-injected rats. The latter increase was totally abolished in animals having received propranolol or yohimbine. The activity of LPL in WAT, heart, and red VLM was approximately 35% lower in exercised rats than in resting animals. Serum triacylglycerols were also reduced by the run. Neither propranolol nor yohimbine interfered with any of these reductions. Exercise did not change serum glucose levels in saline-injected rats but decreased it in those injected with propranolol or yohimbine. Serum insulin was unchanged by exercise and by the antagonists. These findings suggest that the beta- and alpha 2-adrenergic pathways, as well as the exercise-induced rise in serum levels of NEFA, are not responsible for the early reducing effect of a 1-h run on tissue LPL activity in untrained rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Attenuation of the Meal-Induced Increase in Plasma Lipids and Adipose Tissue Lipoprotein Lipase by Guar Gum in Rats

This study was designed to evaluate the effect of guar gum on the postprandial increase in plasma lipids, insulin and lipoprotein lipase (LPL) activity in white adipose tissue (WAT). Male rats were given ad libitum access to purified diets containing either no fiber or 5% guar gum for 3 wk. The animals were killed at various times after a meal (10% of daily ad libitum intake of their respective diets). Consumption of guar gum resulted in smaller final body weight (-7%, P less than 0.05) and ad libitum food intake (-10%, P less than 0.05). The difference in epididymal WAT weight induced by the concomitant diet was relatively larger (-29%, P less than 0.05) than that of whole body weight. Although no difference was seen in fasting plasma total and high density lipoprotein cholesterol levels between dietary groups, the postprandial increase in these variables was larger in the animals given the fiber-free meal than in those receiving the fiber-supplemented meal (P less than 0.01). Guar also attenuated the postprandial rise in plasma triacylglycerols. The presence of fiber in the meal reduced the postprandial increase in plasma insulin (P less than 0.01). The meal-induced rise in LPL activity of WAT was significantly smaller (P less than 0.02) in the animals fed the diet containing fiber than in those receiving the fiber-free diet. Thus, guar gum altered the activity of LPL in WAT, an effect that may be related to the insulin response to this dietary component.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of norepinephrine and denervation on brown adipose tissue in Syrian hamsters

Daily injections of either 0.8 or 3.2 mg norepinephrine (NE)/kg for 2 wk failed to stimulate brown adipose tissue (BAT) growth, GDP binding, or cytochrome-c oxidase activity (COA) in Syrian hamsters (Mesocricetus auratus). However, a single injection of 1.6 mg NE/kg produced a small (23%) but significant acute increase in BAT GDP binding without affecting COA. Thus there is some loss of sensitivity to NE with chronic treatment in Syrian hamsters. Unilateral sympathectomy by surgical denervation of the interscapular BAT (IBAT) resulted in decreased GDP binding and COA in the denervated pad. Chronic NE treatment in hamsters with denervated IBAT only partially reversed the denervation-induced decreases in GDP binding and COA. It therefore appears that NE is not solely responsible for the maintenance and stimulation of thermogenic activity and COA in Syrian hamster BAT. Denervation of IBAT also resulted in elevated levels of lipoprotein lipase (LPL) in this tissue, a surprising finding since brown and white adipose tissue LPL activity were both stimulated by chronic NE treatment. Therefore, although NE has a stimulatory effect on LPL activity, the primary influence of the neural input to IBAT on this enzyme is inhibitory. These data exemplify dramatic differences between rats and hamsters in the mechanisms controlling BAT thermogenesis and white and brown adipose tissue LPL activity.

Lipectomy influences white adipose tissue lipoprotein lipase activity and plasma triglyceride levels in ground squirrels

Golden-mantled ground squirrels undergo marked fattening and fat depletion during the prehibernatory and hibernatory phases, respectively, of their annual body weight cycle. Fat regulation was studied by surgical removal (lipectomy) of most of the inguinal-subcutaneous, retroperitoneal, and parametrial fat depots from female squirrels during the weight-gain phase of the annual cycle. Seven weeks after surgery, body weights of lipectomized (Lipx) and Sham-Lipx squirrels were equivalent, although white adipose tissue was not completely recovered in Lipx animals. Lipoprotein lipase (LPL) activity was markedly elevated in subcutaneous adipose tissue of Lipx squirrels, but not in other depots. Plasma triglyceride (TG) levels also were higher in Lipx squirrels 7 weeks after surgery. Changes in LPL activity and plasma TG may contribute to body mass and lipid restoration following lipectomy.

Plasma lipoprotein cholesterol and triglycerides and lipoprotein lipase activity in epididymal white adipose tissue of rats fed high sucrose or high corn oil diets.

The present study was undertaken to compare plasma lipoprotein lipid composition, as well as white adipose tissue lipoprotein lipase activity, in rats fed purified diets high in either sucrose or corn oil. The experimental diets (65% of calories as sucrose or corn oil, 15% as the opposite nutrient, and 20% as casein) were given ad libitum for 4 weeks. An additional group was fed a nonpurified diet as a reference diet. Both sucrose and oil diets were spontaneously consumed in isocaloric amounts by the animals. Despite energy intakes that were 35% lower than that of the reference group, the sucrose and oil groups exhibited final body weights that were only 6 and 9% lower, respectively, than that of the reference group, and accumulated more fat in the epididymal depots. Postprandial as well as fasting total cholesterol levels were similar in the sucrose and oil groups, while the high-density lipoprotein to total cholesterol ratio was highest in the animals fed corn oil. In both the fasted and fed states, plasma total triglyceride levels were 73% higher in the sucrose group than in the corn oil group. The largest triglyceride differences due to diet were observed in the chylomicron + very-low-density lipoprotein fraction. The oil-fed rats accumulated large amounts of triglycerides in their livers. Postprandial lipoprotein lipase activity in epididymal adipose tissue was almost twice as high in the sucrose group as in the oil group.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperalphalipoproteinaemic activity of BRL 26314—I: Enhanced cholesterol turnover in rats

Administration of BRL 26314 [ N-(4-chlorobenzyl)- l-phenylalanine] raises circulating high-density lipoprotein (HDL) cholesterol and lowers total triglyceride levels in rats whether maintained on stock or semi-synthetic diets. HDL is also elevated by BRL 26314 in hypothyroid rats and in rats with pre-existing hyperlipidaemia where aortic total cholesterol concentration is decreased. BRL 26314 promotes the excretion of a dose of radiolabelled cholesterol as faecal sterols and bile acids, and decreases the extent of cholesterol-radiolabelling in tissue pools, particularly the aorta and adipose tissue. The increase in cholesterol and bile acid (cholic acid) turnover distinguishes BRL 26314 from a cholestatic agent such as 1-naphthyl isothiocyanate where a superficially similar change in HDL concentration disguises an impaired cholesterol transport. BRL 26314 is not a general protein inducer but part of the mechanism of action may involve enhancement of white adipose tissue lipoprotein lipase activity.