Differential expression of lipid metabolism-related genes and myosin heavy chain isoform genes in pig muscle tissue leading to different meat quality

The aim of this study was to investigate the variations in meat quality, lipid metabolism-related genes, myosin heavy chain (MyHC) isoform genes and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) gene mRNA expressions in longissimus dorsi muscle (LM) of two different pig breeds. Six Rongchang and six Landrace barrows were slaughtered at 161 days of age. Subsequently, meat quality traits and gene expression levels in LM were observed. Results showed that Rongchang pigs not only exhibited greater pH, CIE a*_{24 h} and intramuscular fat content but also exhibited lower body weight, carcass weight, dressing percentage, LM area and CIE b*_{24 h} compared with Landrace pigs (P<0.05). Meanwhile, the mRNA expression levels of the lipogenesis (peroxisome proliferator-activated receptor gamma, acetyl-CoA carboxylase and fatty acid synthase) and fatty acid uptake (lipoprotein lipase)-related genes were greater in the Rongchang (P<0.05), whereas the lipolysis (adipose triglyceride lipase and hormone sensitive lipase) and fatty acid oxidation (carnitine palmitoyltransferase-1B)-related genes were better expressed in the Landrace. Moreover, compared with the Landrace, the mRNA expression levels of MyHCI, MyHCIIa and MyHCIIx were greater, whereas the mRNA expression levels of MyHCIIb were lower in the Rongchang pigs (P<0.05). In addition, the mRNA expression levels of PGC-1α were greater in Rongchang pigs than in the Landrace (P<0.05), which can partly explain the differences in MyHC isoform gene expressions between Rongchang and Landrace pigs. Although the small number of samples does not allow to obtain a definitive conclusion, we can suggest that Rongchang pigs possess better meat quality, and the underlying molecular mechanisms responsible for the better meat quality in fatty pigs may be partly due to the higher mRNA expression levels of lipogenesis and fatty acid uptake-related genes, as well as the oxidative and intermediate muscle fibers, and due to the lower mRNA expression levels of lipolysis and fatty acid oxidation-related genes, as well as the glycolytic muscle fibers.     

Dietary l-arginine supplementation differentially regulates expression of lipid-metabolic genes in porcine adipose tissue and skeletal muscle

Obesity is a major health crisis worldwide and new treatments are needed to fight this epidemic. Using the swine model, we recently reported that dietary l-arginine (Arg) supplementation promotes muscle gain and reduces body-fat accretion. The present study tested the hypothesis that Arg regulates expression of key genes involved in lipid metabolism in skeletal muscle and white adipose tissue. Sixteen 110-day-old barrows were fed for 60 days a corn- and soybean-meal-based diet supplemented with 1.0% Arg or 2.05% l-alanine (isonitrogenous control). Blood samples, longissimus dorsi muscle and overlying subcutaneous adipose tissue were obtained from 170-day-old pigs for biochemical studies. Serum concentrations of leptin, alanine and glutamine were lower, but those for Arg and proline were higher in Arg-supplemented pigs than in control pigs. The percentage of oleic acid was higher but that of stearic acid and linoleic acid was lower in muscle of Arg-supplemented pigs, compared with control pigs. Dietary Arg supplementation increased mRNA levels for fatty acid synthase in muscle, while decreasing those for lipoprotein lipase, glucose transporter-4, and acetyl-coenzyme A carboxylase-α in adipose tissue. Additionally, mRNA levels for hormone sensitive lipase were higher in adipose tissue of Arg-supplemented pigs compared with control pigs. These results indicate that Arg differentially regulates expression of fat-metabolic genes in skeletal muscle and white adipose tissue, therefore favoring lipogenesis in muscle but lipolysis in adipose tissue. Our novel findings provide a biochemical basis for explaining the beneficial effect of Arg in improving the metabolic profile in mammals (including obese humans).     

Lipogenic enzyme activities in subcutaneous adipose tissue and skeletal muscle from neonatal pigs consuming maternal or formula milk

The influence of maternal and formula milk on lipid metabolism was studied in 7-day-old pigs. Lipid content, fatty acid composition, lipogenic enzyme activities and expression of GLUT4 mRNA were determined in subcutaneous adipose tissue and skeletal muscle from pigs that were bottle-fed formula milk (F) or sow milk (SM), or were sow-reared (SR). Bottle-fed pigs were isoenergetically fed and achieved similar daily body weight gain. SR pigs have a higher (P < 0.05) body weight gain than bottle-fed pigs. Lipid content of adipose tissue was lower (P < 0.05) in F than in SM and SR pigs. In muscle, lipid content did not differ significantly between groups. In adipose tissue, acetyl-CoA-carboxylase (CBX), fatty acid synthase (FAS), malic enzyme (ME), glucose-6-phosphate-dehydrogenase (G6PDH) and lipoprotein lipase (LPL) activities and GLUT4 mRNA levels were higher (P < 0.05) in SR than in bottle-fed pigs. In muscle, ME and G6PDH activities and GLUT4 mRNA were higher (P < 0.05) in F than in SM and SR pigs; LPL was not detected. The present study indicates that lipogenic enzyme activities and GLUT4 mRNA expression are regulated differently in subcutaneous adipose tissue and skeletal muscle in the neonatal pig.     

The novel gene pFAM134B positively regulates fat deposition in the subcutaneous fat of Sus scrofa

In this study, we analyzed the global gene expression profiles in the subcutaneous fat (SAT) of Jinhua pigs and Landrace pigs at 90 d. Several genes were significantly highly expressed in Jinhua pigs, including genes encoding the rate limiting enzymes in the TCA cycle, fatty acid activation, fatty acid synthesis and triglyceride synthesis. We identified a novel gene tagged by the EST sequences as public No. BF702245.1, which was named porcine FAM134B (pFAM134B) and the pFAM134B mRNA levels of SAT was significantly higher in Jinhua pigs than that in Landrace pigs at 90 d (P < 0.01). Then the effects of pFAM134B on lipid accumulation were investigated by using RNAi and gene overexpression in the subcutaneous adipocytes. The results showed that pFAM134B played a significant positive role in regulating lipid deposition by increasing the mRNA levels of PPARγ, lipogenic genes fatty acid synthetase (FAS) and acetyl-CoA carboxylase (ACC) (P < 0.01) and reducing the mRNA levels of adipose triglyceride lipase (ATGL) and lipase, hormone-sensitive (HSL) (P < 0.01). This study implied that pFAM134B might be a positive factor in lipid deposition, providing insight into the control of fat accumulation and lipid-related disorders.     

Effects of immunization against GnRH on gonadotropins, the GH-IGF-I-axis and metabolic parameters in barrows

Surgically castrated male piglets (barrows) reveal an increase in LH and a decrease in GH compared to untreated boars. Boars that were castrated by immunization against gonadotropin releasing hormone (GnRH) have decreased LH but maintain GH. The difference in GH levels between barrows and immunological castrated boars cannot be explained by testicular steroids because they are low in surgical and immunocastrated boars as well. Therefore, differences in GH concentrations might be due to an interaction between GnRH and growth hormone releasing hormone (GRH) in the hypothalamus or the pituitary. This hypothesis was tested with twelve male piglets that had been castrated within 1 week postnatally and fitted with indwelling cephalic vein catheters at 17 weeks of age. They were split into a control group and an immunized group (each n = 6). Vaccination with Improvac® was performed at 18 and 22 weeks of age. Specific radioimmunoassays were used for hormone determinations (GH, LH, FSH, testosterone and IGF-I). Additionally, metabolic responses were evaluated by measuring analytical parameters that characterize protein synthesis and breakdown, and body fat content. The second vaccination led to a rapid decrease of LH below the limit of detection whereas FSH decreased more slowly, over a period of 5 weeks, from 2.2 to 0.5 ng/ml. This level of FSH, which corresponds to boar-specific concentrations, was maintained thereafter. GH decreased with increasing age but was not influenced by vaccination and remained at a low concentration typical for barrows. Similarly, IGF-I was not altered by vaccination. Consequently, metabolic status was not changed by immunization. It is concluded that the difference in GH levels between surgical and immunocastrated boars is not explained by an interaction between GnRH and GRH.     

Reproductive status effects of pair-housed male pigs on natural,agonistic and sexual behaviours

Boar rearing, which avoids pain and suffering caused by surgical castration, provides better performance, a greater deposition of muscle tissue and leaner carcasses and thus has beneficial effects on both animal welfare and the product. Some countries that do not slaughter boars must consider their boar taint and aggressive and sexual behaviours. Considering that pigs are housed in large groups, which may complicate the formation of social hierarchies and increase fighting and mounting behaviours, some studies have conducted research with reduced numbers of pigs per pen, but these behaviours continued to be observed. However, a study of the reproductive status of pair-housed male pigs has yet to be reported. The aim of this study was to determine whether the reproductive status of uncastrated, immunocastrated and surgically castrated pair-housed male pigs alters their natural, agonistic and sexual behaviours. A total of 48 male pigs from Agroceres PIC™ genetics were assigned to three groups: surgically castrated (barrows), immunocastrated and uncastrated (boars). Natural, aggressive and sexual behaviours of the pigs were assessed by direct observations during four periods of 12 h each (six, five and three weeks before slaughter and the slaughter week). The pigs were housed in pairs from the growing phase until slaughter. Animal behaviour was observed from the finishing phase to slaughter. Carcass lesions were assessed according to five different classes (one: no injury; two to five: severely injured). Overall, boars spent more time lying and less time eating and drinking than barrows. In total of all the periods (48 h), boars expressed more aggressive and sexual behaviours than barrows, whereas immunocastrated pigs displayed similar behaviours to boars, before and after the second vaccine dose. No differences in carcass lesions between treatments and no prevalence of carcasses with severe injuries were observed. In conclusion, the reproductive status of pair-housed male pigs did not change the natural behaviour of boars, immunocastrated pigs or barrows. The agonistic and sexual behaviours of boars and barrows remained unchanged. When housing pigs in pairs, immunocastrated pigs presented similar agonistic and sexual behaviours to boars before and after the second immunocastration vaccine dose. The use of pair-housed uncastrated male pigs has generated welfare benefits for these animals, as the number of carcasses with injuries did not differ from barrows and immunocastrated pigs.     

The role of neutral lipases in human adipose tissue lipolysis

PURPOSE OF REVIEW: The aim of this article is to describe the relative roles of hormone sensitive lipase and adipose triglyceride lipase in human fat cell lipolysis. RECENT FINDINGS: Until recently, only hormone sensitive lipase was considered important for the regulation of lipolysis within fat cells. Recent rodent studies have suggested that adipose triglyceride lipase may, however, be more important. The few human adipose triglyceride lipase studies that have been published point to species differences between humans and rodents. Selective inhibition of hormone sensitive lipase in human fat cells completely counteracts hormone-activated lipolysis, though there is a considerable (>50%) residual nonhormonal (basal) lipolysis. In rodents, adipose triglyceride lipase enzyme activity is stimulated by a cofactor termed CGI-58. In the absence of CGI-58, lipase activity in fat cells is much higher for hormone sensitive lipase than adipose triglyceride lipase. Hormone sensitive lipase expression is regulated by obesity and body weight reduction (decreased and increased, respectively), but this is not the case for adipose triglyceride lipase. A role of adipose triglyceride lipase in human lipolysis is suggested by studies of gene polymorphisms. SUMMARY: Two lipases the 'old' hormone sensitive lipase and the 'new' adipose triglyceride lipase are of importance for the regulation of lipolysis in rodent fat cells. In humans, adipose triglyceride lipase seems essential for maintaining basal lipolytic activity, while hormone sensitive lipase is the enzyme most responsive to stimulated lipolysis.     

Alteration in body composition in the portacaval anastamosis rat is mediated by increased expression of myostatin

The portacaval anastamosis (PCA) rat is a model to examine nutritional consequences of portosystemic shunting in cirrhosis. Alterations in body composition and mechanisms of diminished fat mass following PCA were examined. Body composition of male Sprague-Dawley rats with end-to-side PCA and pair-fed sham-operated (SO) controls were studied 3 wk after surgery by chemical carcass analysis (n=8 each) and total body electrical conductivity (n=6 each). Follistatin, a myostatin antagonist, or vehicle was administered to PCA and SO rats (n=8 in each group) to examine whether myostatin regulated fat mass following PCA. The expression of lipogenic and lipolytic genes in white adipose tissue (WAT) was quantified by real-time PCR. Body weight, fat-free mass, fat mass, organ weights, and food efficiency were significantly lower (P < 0.001) in the PCA than SO rats. Adipocyte size and triglyceride content of epididymal fat in PCA rats were significantly lower (P < 0.01) than in SO rats. Myostatin expression was higher in the WAT of PCA compared with SO rats and was accompanied by an increase in phospho-AMP kinase Thr(172). Follistatin increased whole body fat and WAT mass, adipocyte size, and expression of lipogenic genes in WAT in PCA, but not in SO rats. Myostatin and phospho-AMP kinase protein and lipolytic gene expression were lower with follistatin. We conclude that PCA results in loss of fat mass due to an increased expression of myostatin in adipose tissue with lower lipogenic and higher fatty acid oxidation gene expression.     

Lipolysis: pathway under construction

PURPOSE OF REVIEW: The lipolytic catabolism of stored fat in adipose tissue supplies tissues with fatty acids as metabolites and energy substrates during times of food deprivation. This review focuses on the function of recently discovered enzymes in adipose tissue lipolysis and fatty acid mobilization. RECENT FINDINGS: The characterization of hormone-sensitive lipase-deficient mice provided compelling evidence that hormone-sensitive lipase is not uniquely responsible for the hydrolysis of triacylglycerols and diacylglycerols of stored fat. Recently, three different laboratories independently discovered a novel enzyme that also acts in this capacity. We named the enzyme 'adipose triglyceride lipase' in accordance with its predominant expression in adipose tissue, its high substrate specificity for triacylglycerols, and its function in the lipolytic mobilization of fatty acids. Two other research groups showed that adipose triglyceride lipase (named desnutrin and Ca-independent phospholipase A2zeta, respectively) is regulated by the nutritional status and that it might exert acyl-transacylase activity in addition to its activity as triacylglycerol hydrolase. Adipose triglyceride lipase represents a novel type of 'patatin domain-containing' triacylglycerol hydrolase that is more closely related to plant lipases than to other known mammalian metabolic triacylglycerol hydrolases. SUMMARY: Although the regulation of adipose triglyceride lipase and its physiological function remain to be determined in mouse lines that lack or overexpress the enzyme, present data permit the conclusion that adipose triglyceride lipase is involved in the cellular mobilization of fatty acids, and they require a revision of the concept that hormone-sensitive lipase is the only enzyme involved in the lipolysis of adipose tissue triglycerides.     

Growth hormone-mediated breakdown of body fat: effects of GH on lipases in adipose tissue and skeletal muscle of old rats fed different diets.

Lipid storage and breakdown is mainly controlled by lipoprotein lipase and hormone-sensitive lipase. The aim of this work was to elucidate whether growth hormone mediated loss of adipose tissue involves a concerted action on tissue lipases, and to what degree such events are modulated by dietary regimen. Twelve-month-old rats fed first a high-fat diet or a low-fat diet for 14 weeks were injected with saline or growth hormone (4 mg/kg/d) for four days or three weeks in different combinations with either high- or low-fat diets. In adipose tissue, growth hormone generally inhibited lipoprotein lipase and also attenuated the inhibiting effect of insulin on hormone-sensitive lipase activity. Growth hormone treatment combined with restricted high-fat feeding reduced the activity of both lipases in adipose tissue and stimulated hormone-sensitive lipase in muscle. Generally, plasma levels of free fatty acids, glycerol and cholesterol were reduced by growth hormone, and in combination with restricted high-fat feeding, triglyceride levels improved too. We conclude that growth hormone inhibits lipid storage in adipose tissue by reducing both lipoprotein lipase activity and insulin's inhibitory action on hormone-sensitive lipase. We also propose that growth hormone's effects on tissue lipases and blood lipids are modulated by dietary regimen.     

Fat metabolism is regulated by altered gene expression of lipogenic enzymes and regulatory factors in liver and adipose tissue but not in semimembranosus muscle of pigs during the fattening period

It has been shown previously that lipid metabolism is regulated by fatty acids (FA) and that thyroid hormones are important regulators of energy metabolism. The effects of weight, dietary fat level and dietary FA profile on thyroid hormone levels and expression of lipogenic genes and tissue FA composition were studied. Sixty-one crossbred gilts weighing 62 ± 5.2 kg BW average were either slaughtered at the beginning of the trial (n = 5) or fed one of seven diets (n = 8 pigs per diet): a semi-synthetic diet formulated to contain a very low level of fat (NF) and six diets based on barley-soybean meal supplemented with approximately 10% fat of different origin and slaughtered at 100 kg BW. The supplemental fats were tallow, high-oleic sunflower oil, sunflower oil (SFO), linseed oil, fat blend (55% tallow, 35% sunflower oil, 10% linseed oil) and fish oil blend (40% fish oil, 60% linseed oil). In general, the dietary FA profiles altered the FA composition of liver, semimembranosus muscle and adipose tissues. Pigs fed the NF diet had the highest free and total triiodothyronine (T3) values followed by pigs fed SFO. Total T3 levels were higher in pigs at 60 kg than in pigs at 100 kg. Correlations between thyroid hormones and genes encoding enzymes of fat synthesis in adipose tissue (acetyl CoA carboxylase (ACACA), fatty acid synthase and stearoyl CoA desaturase (SCD)) and the large differences in expression of lipogenic genes at different weights (60 and 100 kg BW), suggest a role for thyroid hormones and for T3, in particular, in regulating whole animal fat metabolism, with effects brought about by altered expression of lipogenic genes. Liver sterol receptor element binding protein-1 (SREBP1) mRNA content was affected by dietary treatment (P < 0.001) and was correlated with ACACA and SCD, whereas adipose tissue SREBP1 was not correlated with the mRNA abundance of any lipogenic enzyme. Weight and tissue factors showed greater influence on mRNA abundance of genes related with lipid metabolism than diet and tissue FA composition. In the pig, FA synthesis appear to be of greater magnitude in adipose tissue than in the liver as suggested by the higher expression of lipogenic genes in adipose tissue.     

The influence of preadipocyte differentiation capacity on lipolysis in human mature adipocytes.

The ability of catecholamines to maximally stimulate adipocyte lipolysis (lipolytic capacity) is decreased in obesity. It is not known whether the lipolytic capacity is determined by the ability of adipocytes to differentiate. The aim of the study was to investigate if lipolytic capacity is related to preadipocyte differentiation and if the latter can predict lipolysis in mature adipocytes. IN VITRO experiments were performed on differentiating preadipocytes and isolated mature adipocytes from human subcutaneous adipose tissue. In preadipocytes, noradrenaline-induced lipolysis increased significantly until terminal differentiation (day 12). However, changes in the expression of genes involved in lipolysis (hormone sensitive lipase, adipocyte triglyceride lipase, the alpha2-and beta1-adrenoceptors, perilipin, and fatty acid binding protein) reached a plateau much earlier during differentiation (day 8). A significant positive correlation between lipolysis in differentiated preadipocytes and mature adipocytes was observed for noradrenaline (r=0.5, p<0.01). The late differentiation capacity of preadipocytes measured as glycerol-3-phosphate dehydrogenase activity was positively correlated with noradrenaline-induced lipolysis in preadipocytes (r=0.51, p<0.005) and mature fat cells (r=0.35, p<0.05). In conclusion, intrinsic properties related to terminal differentiation determine the ability of catecholamines to maximally stimulate lipolysis in fat cells. The inability to undergo full differentiation might in part explain the low lipolytic capacity of fat cells among the obese.     

Methionine restriction effects on 11 -HSD1 activity and lipogenic/lipolytic balance in F344 rat adipose tissue

Methionine restriction (MR) limits age-related adiposity in Fischer 344 (F344) rats. To assess the mechanism of adiposity resistance, the effect of MR on adipose tissue (AT) 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD1) was examined. MR induced 11beta-HSD1 activity in all ATs, correlating with increased tissue corticosterone. However, an inverse relationship between 11beta-HSD1 activity and adipocyte size was observed. Because dietary restriction controls lipogenic and lipolytic rates, MR's effects on lipogenic and lipolytic enzymes were evaluated. MR increased adipose triglyceride lipase and acetyl-coenzyme A carboxylase (ACC) protein levels but induced ACC phosphorylation at serine residues that render the enzyme inactive, suggesting alterations of basal lipolysis and lipogenesis. In contrast, no changes in basal or phosphorylated hormone-sensitive lipase levels were observed. ACC-phosphorylated sites were specific for AMP-activated protein kinase (AMPK); therefore, AMPK activation was evaluated. Significant differences in AMPKalpha protein, phosphorylation, and activity levels were observed only in retroperitoneal fat from MR rats. No differences in protein kinase A phosphorylation and intracellular cAMP levels were detected. In vitro studies revealed increased lipid degradation and a trend toward increased lipid synthesis, suggesting the presence of a futile cycle. In conclusion, MR disrupts the lipogenic/lipolytic balance, contributing importantly to adiposity resistance in F344 rats.     

Adipocyte triglyceride lipase expression in human obesity

We have investigated the gene and protein expression of adipose triglyceride lipase (ATGL) and triglyceride (TG) lipase activity from subcutaneous and visceral adipose tissue of lean and obese subjects. Visceral and subcutaneous adipose tissue was obtained from 16 age-matched lean and obese subjects during abdominal surgery. Tissues were analyzed for mRNA expression of lipolytic enzymes by real-time quantitative PCR. ATGL protein content was assessed by Western blot and TG lipase activity by radiometric assessment. Subcutaneous and visceral adipose tissue of obese subjects had elevated mRNA expression of PNPLA2 (ATGL) and other lipases including PNPLA3, PNPLA4, CES1, and LYPLAL1 (P < 0.05). Surprisingly, ATGL protein expression and TG lipase activity were reduced in subcutaneous adipose tissue of obese subjects. Immunoprecipitation of ATGL reduced total TG lipase activity in adipose lysates by 70% in obese and 83% in lean subjects. No significant differences in the ATGL activator CGI-58 mRNA levels (ABHD5) were associated with obesity. These data demonstrate that ATGL is important for efficient TG lipase activity in humans. They also demonstrate reduced ATGL protein expression and TG lipase activity despite increased mRNA expression of ATGL and other novel lipolytic enzymes in obesity. The lack of correlation between ATGL protein content and in vitro TG lipase activity indicates that small decrements in ATGL protein expression are not responsible for the reduction in TG lipase activity observed here in obesity, and that posttranslational modifications may be important.     

Castration-induced changes in microRNA expression profiles in subcutaneous adipose tissue of male pigs

MicroRNAs (miRNAs) are class of molecular regulators found to participate in numerous biological processes, such as adipogenesis and obesity in mammals. To determine the roles of miRNAs involved in castration-induced body fatness, we investigated the different miRNA expression patterns in subcutaneous adipose tissue between intact and castrated male pigs. Our results showed that castration led to decrease serum testosterone but increase serum Leptin levels (P?<?0.01). Moreover, castration also increased adipocyte size, body fat content and backfat thickness in male pigs (P?<?0.01). Meanwhile, miRNA expression profiles in adipose tissue were changed by castration, and 18 miRNAs were considered as the differentially expressed candidates between intact and castrated male pigs. Furthermore, functional analysis indicated that the differential expressed miRNAs and their target genes are involved in the regulation of fatty acid metabolism. In brief, our present study provides a comprehensive view on how miRNAs works in subcutaneous adipose tissue with castration. These results suggested that miRNAs might play an important role in the castration-induced fat deposition in male pigs.     

Considerations on the performance of immunocastrated male pigs

With the ongoing social pressure on surgical castration of pigs, an increase in the population of pigs that are either not castrated or immunocastrated (IC) can be expected. In both cases, their nutrient requirements and performance will differ from surgically castrated pigs and will require changes in their management. Immunocastration is performed by giving two injections of a modified gonadotrophin-releasing hormone component along with an adjuvant, at least 4 weeks apart. This paper describes the reported differences in growth performance and carcass quality of IC male pigs in comparison with boars (BO) and barrows (BA). Theoretically, IC pigs remain physiologically boar until the second vaccination and therefore, growth may be comparable with BO until this second vaccination. From then on, IC male pigs consume more feed than BO and grow faster when fed ad libitum. IC showed a faster growth and better feed conversion ratio than BA. When fed restrictedly, BO grow faster and more efficiently than BA and IC. IC have a lower carcass yield than BA and BO, whereas meat percentage is intermediate.     

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.     

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) reduces lipoprotein lipase activity in the adipose tissue of the guinea pig

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) administered to young male guinea pigs at a dose of 1 microgram/kg (single intraperitoneal injection) caused a large reduction in adipose tissue lipoprotein lipase (LPL) activity. This effect occurred rapidly; a 70% decrease was noticed after 24 hour and 80% of LPL activity was lost by 48 hours when the serum triglyceride levels increased to 175% of control levels. LPL is known to play an important role in controlling the amount of free fatty acids supplied to adipose tissues. Administration of a large dose of glucose to fasted guinea pigs, which have shown a similar weight loss, but less LPL loss than TCDD-treated animals, had the effect of elevating their adipose LPL levels back to a near normal level, whereas the same treatment caused no significant increase in the LPL levels of TCDD-treated animals. Evidence indicates that the TCDD-caused decline in LPL activity is irreversible. As a consequence, the affected guinea pigs are incapable of responding to changes in nutritional status.