Adipose Tissue Lipoprotein Lipase Research Articles

Decoding the role of angiopoietin-like protein 4/8 complex–mediated plasmin generation in the regulation of LPL activity

After feeding, adipose tissue lipoprotein lipase (LPL) activity should be maximized, therefore the potent LPL-inhibitory activity of angiopoietin-like protein 4 (ANGPTL4) must be blocked by ANGPTL8 through formation of ANGPTL4/8 complexes. ANGPTL4/8 tightly binds and protects LPL but also partially inhibits its activity. Recently, we demonstrated ANGPTL4/8 also binds tissue plasminogen activator (tPA) and plasminogen to generate plasmin that cleaves ANGPTL4/8 to restore LPL activity. Although fully active LPL in the fat postprandially is desirable, ANGPTL4/8 removal could subject LPL to profound inhibition by ANGPTL3/8 (the most potent circulating LPL inhibitor), inhibition by other LPL inhibitors like ANGPTL4, ANGPTL3, and ApoC3 or interfere with ApoC2-mediated LPL activation. To understand better these potential paradoxes, we examined LPL inhibition by ANGPTL3/8, ANGPTL4, ANGPTL3, and ApoC3 and LPL stimulation by ApoC2 in the presence of ANGPTL4/8 + tPA + plasminogen. Remarkably, ANGPTL3/8-mediated LPL inhibition was almost completely blocked, with the mechanism being cleavage of fibrinogen-like domain–containing ANGPTL3 present in the ANGPTL3/8 complex. The LPL-inhibitory effects of ANGPTL4, ANGPTL3, and ApoC3 were also largely reduced in the presence of ANGPTL4/8 + tPA + plasminogen. In contrast, the ability of ApoC2 to stimulate LPL activity was unaffected by ANGPTL4/8-mediated plasmin generation. Together, these results explain how plasmin generated by increased postprandial ANGPTL4/8 levels in adipose tissue enables maximal LPL activity by preventing ANGPTL3/8, ANGPTL4, ANGPTL3, and ApoC3 from inhibiting LPL, while permitting ApoC2-mediated LPL activation to occur.

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)

Abstract 161: Ablation Of Intracellular Lipolytic Inhibitor G0S2 Promotes Vascular Lipolysis And Alleviates Diet-induced Atherosclerosis

Adipose tissue plays a central role in the regulation of plasma triglyceride (TG) and fatty acid (FA) levels, whose elevation is associated with atherosclerotic cardiovascular disease (ASCVD). Circulating TGs are hydrolyzed by lipoprotein lipase (LPL), releasing FAs that are taken up by adipocytes. Conversely, lipolytic action of adipose tissue triglyceride lipase (ATGL) mobilizes intracellular TG storage, supplying FAs via circulation for utilization by other tissues. However, how intracellular lipolysis influences intravascular lipolysis and atherosclerotic development remains largely unknown. Herein, the current study aimed to explore the role of G0S2, a selective protein inhibitor of ATGL, in this particular context. When treated with a Western diet and antisense oligonucleotides (ASOs) targeting LDLR, mice with a global ablation of G0S2 exhibited a significantly reduced lesion formation in aorta and brachiocephalic artery than their wild type (WT) littermates. Despite of little to no impact on hypercholesterolemia, total plasma and lipoprotein-specific TG content were normalized in G0S2 -/- mice. While it did not elicit any effects on intestinal lipid adsorption and hepatic TG secretion, the G0S2 ablation resulted in considerable elevation of LPL activity and protein levels in both plasma and adipose tissue. Accordingly, these G0S2 -/- mice showed a greatly improved TG clearance upon an oral lipid challenge. Interestingly, transplantation of G0S2 -/- adipose tissue increased circulating LPL in the WD-treated WT mice, which subsequently displayed a profound reduction of plasma TG levels as well as alleviation of hepatic steatosis. By studying adipose tissue explants and primary adipocytes, we observed that the G0S2 ablation led to markedly improved insulin sensitivity, resulting in increased FOXO1 phosphorylation and decreased expression of the LPL inhibitor ANGPTL4. Together, our data indicate that in the absence of G0S2, upregulation of adipose tissue LPL plays an important role in the clearance of circulating TGs and alleviation of diet-induced hypertriglyceridemia and atherosclerosis. We thus conclude that adipocyte G0S2 acts as a critical switch of both intracellular and vascular lipolysis.

Effect of Cold Exposure and Exercise on Insulin Sensitivity and Serum Free Fatty Acids in Obese Rats.

This study aimed to explore the effect of exercise and cold exposure on insulin sensitivity and the level of serum free fatty acids (FFA) in diet-induced obese rats. Sixty-four diet-induced obese rats were randomly assigned to eight groups: room temperature-sedentary, room temperature-exercise, acute cold exposure-sedentary, acute cold exposure-exercise, intermittent cold exposure-sedentary, intermittent cold exposure-exercise, sustained cold exposure-sedentary, and sustained cold exposure-exercise. After the interventions, the homeostatic model assessment for insulin resistance (HOMA-IR) values, the level of serum FFA, subcutaneous fat ratio (SFR) and visceral fat ratio, enzyme activities of adipose triglyceride lipase, and lipoprotein lipase (LPL) in inguinal adipose tissue, and protein expression of PGC1-α and p38 MAPK in skeletal muscle were investigated. We found that exercise ( P = 0.0136) and cold exposure ( P < 0.0001) reduced HOMA-IR values independently. Exercise reduced serum FFA ( P = 0.0041), whereas cold exposure did not affect them. Moreover, the HOMA-IR values were positively correlated with the serum FFA levels ( r = 0.32, P = 0.01). SFR or visceral fat ratio was coordinately reduced by the interaction (for SFR, P = 0.0015) or opposing main effects between or of cold exposure and exercise, supporting the reduction of serum FFA. However, cold exposure or exercise increased the activity of adipose triglyceride lipase and LPL independently or interactively (for LPL, P = 0.0143), suggesting an increase in serum FFA. Finally, cold exposure and exercise enhanced protein expression of PGC1-α and p38 MAPK independently or interactively (for p38 MAPK, P = 0.0226), suggesting increased uptake and oxidation of serum FFA in muscle. These results suggest that the combination of exercise and cold exposure may result in more serum FFA utilization than production and thus lead to reduced serum FFA and increased insulin sensitivity.

Gestational Undernutrition and the Development of Obesity in Rats

The effects of early gestational undernutrition and subsequent re-feeding patterns on offspring food intake, body weight and adiposity were examined. Pregnant rats were food restricted to 50% of their preconception intake levels during the first 2 weeks of pregnancy and were then either returned to ad libitum feeding or pair-fed to nonrestricted control rats. Male and female offspring of previously deprived, ad libitum refed mothers gained significantly more weight when fed a standard low fat, high carbohydrate diet than did control offspring. When the maintenance diet was changed at 140 days of age to a high fat diet, both groups of previously deprived male offspring gained weight at greater than control rates. In contrast, the three groups of female rats gained weight at comparable rates after the diet change. Adipocyte hypertrophy and elevated carcass lipid content were seen in high fat—fed male but not female offspring of previously deprived mothers. Adipose tissue lipoprotein lipase activity was unaffected by these manipulations.

Dietary Isoleucine and Valine: Effects on Lipid Metabolism and Ureagenesis in Pigs Fed with Protein Restricted Diets.

A mixture of valine (Val) and isoleucine (Ile) not only decreases the negative impact of very low protein (VLP) diets on the growth of pigs, but also influences the nitrogen (N) balance and lipid metabolism; however, the underlying pathways are not well understood. This study aimed to investigate the effect of dietary Val and Ile on lipogenesis, lipolysis, and ureagenesis under protein restriction. After one week of acclimation, forty three-week-old pigs were randomly assigned to following dietary treatments (n = 8/group) for 5 weeks: positive control (PC): normal protein diet; negative control (NC): VLP diet; HV: NC supplemented with Val; HI: NC supplemented with Ile; and HVI: NC supplemented with both Val and Ile. HVI partially improved the body weight and completely recovered the feed intake (FI) of pigs fed with NC. HVI increased thermal radiation and improved the glucose clearance. HVI had a lower blood triglyceride than PC and blood urea N than NC. NC and HV promoted lipogenesis by increasing the transcript of fatty acid synthase (FAS) in the liver and lipoprotein lipase (LPL) in adipose tissue but reducing hormone-sensitive lipase (HSL) in the liver. HVI reduced the increased rate of lipogenesis induced by the NC group through normalizing the mRNA abundance of hepatic FAS, sterol regulatory element binding transcription factor 1, and HSL and LPL in adipose tissue. NC, HV, HI, and HVI reduced the ureagenesis by decreasing the protein abundance of carbamoyl phosphate synthetase I, ornithine transcarboxylase, and arginosuccinate lyase in the liver. Overall, HVI improved the growth, FI, and glucose clearance, and decreased the rate of lipogenesis induced by VLP diets.

Improved β-cell function leads to improved glucose tolerance in a transgenic mouse expressing lipoprotein lipase in adipocytes

Lipoprotein lipase (LPL) hydrolyzes the triglyceride core of lipoproteins and also functions as a bridge, allowing for lipoprotein and cholesterol uptake. Transgenic mice expressing LPL in adipose tissue under the control of the adiponectin promoter (AdipoQ-LPL) have improved glucose metabolism when challenged with a high fat diet. Here, we studied the transcriptional response of the adipose tissue of these mice to acute high fat diet exposure. Gene set enrichment analysis (GSEA) provided mechanistic insight into the improved metabolic phenotype of AdipoQ-LPL mice. First, the cholesterol homeostasis pathway, which is controlled by the SREBP2 transcription factor, is repressed in gonadal adipose tissue AdipoQ-LPL mice. Furthermore, we identified SND1 as a link between SREBP2 and CCL19, an inflammatory chemokine that is reduced in AdipoQ-LPL mice. Second, GSEA identified a signature for pancreatic β-cells in adipose tissue of AdipoQ-LPL mice, an unexpected finding. We explored whether β-cell function is improved in AdipoQ-LPL mice and found that the first phase of insulin secretion is increased in mice challenged with high fat diet. In summary, we identify two different mechanisms for the improved metabolic phenotype of AdipoQ-LPL mice. One involves improved adipose tissue function and the other involves adipose tissue—pancreatic β-cell crosstalk.

Bioactive lipids and lipoprotein lipase in epicardial adipose tissue from patients with coronary artery disease: Unfolding a missing link

Background and Aims : Epicardial adipose tissue (EAT) contributes to atherosclerotic cardiovascular disease (ASCVD). EAT presents a specific lipidomic signature, with increased proinflammatory lipids, such as ceramides (Cer). Besides the activity of lipoprotein lipase (LPL) in EAT, supplying fatty acids to the tissue, would contribute to its expansion. Our aim was to evaluate links among LPL activity and bioactive lipids in EAT from coronary disease (CAD) patients.

Red-Skin Extracts of Lotus Seeds Alleviate High-Fat-Diet Induced Obesity via Regulating Lipoprotein Lipase Activity

In recent years, obesity has become an epidemic and an important public health concern. This study was designed to explore the anti-obesity effects of red-skin extracts (RSE) from lotus seeds on high-fat-diet (HFD)-fed mice. In this study, a total of 55 phenolic compounds from the RSE were tentatively characterized using a UPLC-Q/TOF-MS system, including 9 phenolic acids and derivatives, 40 flavonoids, 2 proanthocyanidin, and 4 coumarins and derivatives. Our data demonstrated that RSE could significantly ameliorate obesity characteristics of HFD-fed mice by regulating tissue specific lipoprotein lipase (LPL) activities. In detailed, the activity and expression of LPL in adipose tissue was inhibited, and the activity and expression of LPL in skeletal muscle tissue was enhanced. Overall, these findings suggested that RSE from the red skin of lotus seeds could serve as a great candidate for a value-added, functional ingredient due to its anti-obesity effects via the regulation of LPL activity.

Energy Metabolism Changes and Dysregulated Lipid Metabolism in Postmenopausal Women.

Aging women experience hormonal changes, such as decreased estrogen and increased circulating androgen, due to natural or surgical menopause. These hormonal changes make postmenopausal women vulnerable to body composition changes, muscle loss, and abdominal obesity; with a sedentary lifestyle, these changes affect overall energy expenditure and basal metabolic rate. In addition, fat redistribution due to hormonal changes leads to changes in body shape. In particular, increased bone marrow-derived adipocytes due to estrogen loss contribute to increased visceral fat in postmenopausal women. Enhanced visceral fat lipolysis by adipose tissue lipoprotein lipase triggers the production of excessive free fatty acids, causing insulin resistance and metabolic diseases. Because genes involved in β-oxidation are downregulated by estradiol loss, excess free fatty acids produced by lipolysis of visceral fat cannot be used appropriately as an energy source through β-oxidation. Moreover, aged women show increased adipogenesis due to upregulated expression of genes related to fat accumulation. As a result, the catabolism of ATP production associated with β-oxidation decreases, and metabolism associated with lipid synthesis increases. This review describes the changes in energy metabolism and lipid metabolic abnormalities that are the background of weight gain in postmenopausal women.

Angiopoietin-like proteins and postprandial partitioning of fatty acids.

Over the last two decades, evolving discoveries around angiopoietin-like (ANGPTL) proteins, particularly ANGPTL3, ANGPTL4, and ANGPTL8, have generated significant interest in understanding their roles in fatty acid (FA) metabolism. Until recently, exactly how this protein family regulates lipoprotein lipase (LPL) in a tissue-specific manner to control FA partitioning has remained elusive. This review summarizes the latest insights into mechanisms by which ANGPTL3/4/8 proteins regulate postprandial FA partitioning. Accumulating evidence suggests that ANGPTL8 is an insulin-responsive protein that regulates ANGPTL3 and ANGPTL4 by forming complexes with them to increase or decrease markedly their respective LPL-inhibitory activities. After feeding, when insulin levels are high, ANGPTL3/8 secreted by hepatocytes acts in an endocrine manner to inhibit LPL in skeletal muscle, whereas ANGPTL4/8 secreted by adipocytes acts locally to preserve adipose tissue LPL activity, thus shifting FA toward the fat for storage. Insulin also decreases hepatic secretion of the endogenous ANGPTL3/8 inhibitor, apolipoprotein A5 (ApoA5), to accentuate ANGPTL3/8-mediated LPL inhibition in skeletal muscle. The ANGPTL3/4/8 protein family and ApoA5 play critical roles in directing FA toward adipose tissue postprandially. Selective targeting of these proteins holds significant promise for the treatment of dyslipidemias, metabolic syndrome, and their related comorbidities.

Influence of Dietary Chitosan Feeding Duration on Glucose and Lipid Metabolism in a Diabetic Rat Model.

This study was designed to investigate the influence of dietary chitosan feeding-duration on glucose and lipid metabolism in diabetic rats induced by streptozotocin and nicotinamide [a non-insulin-dependent diabetes mellitus (NIDDM) model]. Male Sprague-Dawley rats were used as experimental animals and divided into short-term (6 weeks) and long-term (11 weeks) feeding durations, and each duration contained five groups: (1) control, (2) control + 5% chitosan, (3) diabetes, (4) diabetes + 0.8 mg/kg rosiglitazone (a positive control), and (5) diabetes + 5% chitosan. Whether the chitosan feeding was for 6 or 11 weeks, the chitosan supplementation decreased blood glucose and lipids levels and liver lipid accumulation. However, chitosan supplementation decreased plasma tumor necrosis factor (TNF)-α, insulin levels, alanine aminotransferase (ALT) activity, insulin resistance (HOMA-IR), and adipose tissue lipoprotein lipase activity. Meanwhile, it increased plasma high-density lipoproteins (HDL)-cholesterol level, plasma angiopoietin-like-4 protein expression, and plasma triglyceride levels (at 11-week feeding duration only). Taken together, 11-week (long-term) chitosan feeding may help to ameliorate the glucose and lipid metabolism in a NIDDM diabetic rat model.

Lipoprotein lipase and endothelial lipase behaviour in circulation and epicardial adipose tissue from coronary patients. The role of GPIHBP1

Lipoprotein lipase and endothelial lipase behaviour in circulation and epicardial adipose tissue from coronary patients. The role of GPIHBP1

Real-time imaging of vascular brown adipose tissue lipoprotein lipase activity

Background and Aims: Lipoprotein lipase (LPL) liberates fatty acids and glycerol from the core of triglyceride-rich lipoproteins (TRLs). Delayed postprandial clearance of TRLs is associated with atherosclerosis. Measurement of the effective tissue LPL activity has proven difficult, as not only the intrinsic activity of the enzyme but also the intravascular localization is important for proper TRL processing. We developed an ultrafast confocal in vivo microscopy-based approach for visualizing LPL action in capillaries.

287 Effects of copper hydroxychloride on growth performance and abundance of genes involved in lipid metabolism of growing pigs

Abstract An experiment was conducted to test the hypothesis that Cu hydroxychloride (IntelliBond CII, Micronutrients, LLC, Indianapolis, IN) improves growth performance by upregulating the mRNA transcription of genes involved in lipid metabolism of pigs. Thirty-two pigs (15.05 ± 0.98 kg) were allotted to 2 dietary treatments with 2 pigs per pen for a total of 8 replicate pens per treatment. Pigs were fed a control diet based on corn, soybean meal, and distillers dried grains with solubles that included Cu to meet the requirement. A second diet was formulated by adding 150 mg Cu/kg from Cu hydroxychloride to the control diet. On the last day of the experiment, one pig per pen was sacrificed and samples from liver, skeletal muscle, and subcutaneous adipose tissue were collected to analyze relative mRNA abundance of genes involved in lipid metabolism. Data were analyzed using SAS with pen as the experimental unit. Diet was the fixed effect and replicate was the random effect. Results indicated that overall average daily gain and gain:feed were greater (P &amp;lt; 0.05) for pigs fed the diet containing Cu hydroxychloride compared with pigs fed the control diet (Table 1). Pigs fed the diet supplemented with Cu hydroxychloride had increased (P &amp;lt; 0.05) abundance of cluster of differentiation 36 in liver and increased (P &amp;lt; 0.05) abundance of fatty acid binding protein 4 and lipoprotein lipase in subcutaneous adipose tissue. Inclusion of Cu hydroxychloride also tended to increase (P &amp;lt; 0.10) abundance of fatty acid binding protein 1, peroxisome proliferator-activated receptor alpha, and carnitine palmitoyl transferase 1 B in liver, skeletal muscle, and subcutaneous adipose tissue, respectively. In conclusion, supplementation of Cu hydroxychloride to the control diet improved growth performance and may affect signaling pathways associated with lipid metabolism by upregulating abundance of some genes involved in post-absorptive metabolism of lipids.

Evaluation of Antiobesity Activity of Soybean Meal Products Fermented by Lactobacillus plantarum FPS 2520 and Bacillus subtilis N1 in Rats Fed with High-Fat Diet.

Single strain or mixed strains of Lactobacillus plantarum FPS 2520 and Bacillus subtilis N1 were used to ferment soybean meal (SBM), and the antiobesity activity of the fermented SBM product was investigated in rats fed with high-fat diet (HFD). After fermentation, free amino nitrogen, total peptide, and isoflavone contents were markedly raised, and genistein and daidzein were the major isoflavones in the fermented SBM. After fed with HFD for 10 weeks, obese Sprague-Dawley rats were orally treated with various fermented products for 6 weeks. The body weight gains, as well as weights of abdominal fat and epididymis fat, of rats fed with fermented SBM products were significantly downregulated. The treatment with the mixed-strains fermented SBM product significantly decreased plasma levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol, but increased the level of high-density lipoprotein-cholesterol. Moreover, the levels of TG, TC, fatty acid synthase, and acetyl-CoA carboxylase (ACC) in liver were diminished, and the activities of hormone-sensitive lipase and lipoprotein lipase in adipose tissue were augmented. Taken together, these data demonstrated the antiobesity activity of fermented SBM products, among which the product fermented by the mixed strains being the most effective one. Therefore, these fermented SBM products are potential to be developed as functional foods or additives for treatment of obesity and prevention against obesity-induced complications.

Gochujang prepared using rice and wheat koji partially alleviates high-fat diet-induced obesity in rats.

The aim of this study was to compare whether gochujang products prepared using giant embryo rice koji (rice gochujang, RG) and wheat koji (wheat gochujang, WG) have anti‐obesity effects on rats fed a high‐fat diet (HFD), who served as a model for obesity. The nutritional composition of RG and WG including proximate constituents, amino acid and fatty acid compositions were investigated. Consequently, the secondary fermented metabolites were analyzed in RG and WG by ultrahigh‐performance liquid chromatography and mass spectrometry. Rats were fed a HFD containing 10% RG powder (HFD‐RG) or 10% WG powder (HFD‐WG) for 8 weeks. Body weight gain, weights of liver, epididymal, retroperitoneal, perirenal, and total white fat pads, and levels of serum triglyceride (TG), total cholesterol, low‐density lipoprotein cholesterol, and leptin were lower in all gochujang groups than in the HFD group. Furthermore, RG and WG treatment decreased the hepatic TG content and lipid accumulation and significantly reduced the size of epididymal adipocytes. These effects are probably mediated through inhibition of hepatic fatty acid synthase, acetyl CoA carboxylase, malic enzyme, and adipose tissue lipoprotein lipase activities. The anti‐obesity effect was slightly greater in the HFD‐RG group than in the HFD‐WG group. This effect may be attributed to secondary metabolites, such as capsaicin, genistein, daidzein, soyasaponin, and lysophosphatidylcholines, contained in gochujang prepared using giant embryo rice or wheat koji.

Effects of copper hydroxychloride on growth performance and abundance of genes involved in lipid metabolism of growing pigs.

An experiment was conducted to test the hypothesis that copper (Cu) hydroxychloride improves growth performance by upregulating the mRNA transcription of genes involved in lipid metabolism of pigs fed a diet based on corn, soybean meal (SBM), and distillers dried grains with solubles (DDGS). Thirty-two pigs (15.05 ± 0.98 kg) were allotted to 2 dietary treatments with 2 pigs per pen for a total of 8 replicate pens per treatment. Pigs were fed a corn-SBM-DDGS control diet that included Cu to meet the requirement. A second diet was formulated by adding 150 mg Cu/kg from copper hydroxychloride to the control diet. On the last day of the experiment, one pig per pen was sacrificed, and samples from liver, skeletal muscle, and subcutaneous adipose tissue were collected to analyze relative mRNA abundance of genes involved in lipid metabolism. Results indicated that overall ADG and G:F were greater (P < 0.05) for pigs fed the diet containing copper hydroxychloride compared with pigs fed the control diet. Pigs fed the diet supplemented with copper hydroxychloride also had increased (P < 0.05) abundance of cluster of differentiation 36 in the liver and increased (P < 0.05) abundance of fatty acid-binding protein 4 and lipoprotein lipase in subcutaneous adipose tissue. Inclusion of copper hydroxychloride also tended to increase (P < 0.10) the abundance of fatty acid-binding protein 1, peroxisome proliferator-activated receptor α, and carnitine palmitoyltransferase 1B in the liver, skeletal muscle, and subcutaneous adipose tissue, respectively. This indicates that dietary Cu may affect signaling pathways associated with lipid metabolism by improving the uptake, transport, and utilization of fatty acids. In conclusion, supplementation of copper hydroxychloride to the control diet improved growth performance and upregulated the abundance of some genes involved in postabsorptive metabolism of lipids.

PSXI-27 Association of an increased marbling score by dietary glycerol supplementation with lipid metabolism gene expression in Korean cattle steers

Abstract This study investigated effects of dietary glycerol supplementation on liver, muscle, and adipose gene expression related with gluconeogenesis and lipid metabolism and association of gene expression levels with marbling score in Korean cattle steers. Fourteen Korean cattle steers (average age 28.4 months; average body weight 733 kg) were equally assigned to two groups (0 and 5% glycerol supplementation). Glycerol was provided with glycerol (63%)-adsorbed ground wheat bran (37%, DM) by top dressing during roughage feeding. A concentrate (1.2% of body weight) and 1.0 kg of ryegrass were individually fed twice daily. After four months of study, steers were slaughtered, and marbling score was evaluated. Longissimus thoracis (LT) and subcutaneous adipose tissue at the 13th thoracic vertebra area and liver were collected and analyzed for mRNA levels by quantitative real-time PCR. Statistical significance was analyzed by analysis of variance. Correlations were analyzed using Pearson’s correlation analysis. Glycerol supplementation increased (P = 0.01) marbling score. In the LT, glycerol supplementation tended to increase (0.05 &amp;lt; P ≤ 0.10) lipid uptake CD36 and lipoprotein lipase (LPL) mRNA levels. In subcutaneous adipose tissues, glycerol supplementation increased (P ≤ 0.05) LPL, adipogenic sterol regulatory element binding protein 1 (SREBP1), and lipogenic acetyl CoA carboxylase (ACC) mRNA levels and tended to increase (0.05 &amp;lt; P &amp;lt; 0.10) CD36, adipogenic peroxisome proliferator-activated gamma (PPARG), and lipogenic fatty acid synthase (FASN) expression. It did not affect (P &amp;gt; 0.05) mRNA levels of hepatic gluconeogenesis genes. Marbling score showed significant positive correlations (0.57 &amp;lt; r &amp;lt; 0.68; P &amp;lt; 0.05) with mRNA levels of several genes including LPL, PPARG, SREBP1, and ACC in adipose tissues, but not with any genes examined in the LT. Our study demonstrates that lipid uptake, adipogenesis and lipogenesis may mainly contribute to the increased marbling score by glycerol supplementation.

Histology and molecular biology studies on the expression and localization of angiopoietin-like protein 8 in human tissues.

Angiopoietin-like protein (ANGPTL) 8 regulates the partitioning of triglycerides by inhibiting lipoprotein lipase in muscle and adipose tissues. ANGPTL8 is expressed in the liver and adipose tissue and secreted into the blood. However, the precise localization of ANGPTL8-expressing cells in these tissues remains unknown. The aim of the present study was to investigate the localization of ANGPTL8-expressing cells in human tissues. Using formalin-fixed paraffin-embedded human tissue specimens, the expression of ANGPTL8 was investigated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC) and in situ hybridization (ISH). The expression level of ANGPTL8 mRNA was the highest in the liver, followed by lipoma, hibernoma and normal adipose tissue. In the liver, wild type (KF809856) and two splice variants of ANGPTL8 mRNA (KF809857 and KF809858) were found to be expressed. The expression level of the splice variant KF809858, which produces a short form of ANGPTL8, accounted for <1% of ANGPTL8 in the liver. IHC revealed that ANGPTL8 was expressed in hepatocytes in zone 1 of the hepatic acinus in the liver. In the adipose tissue, mature adipocytes weakly expressed ANGPTL8, while immature adipocytes strongly expressed it. ISH confirmed ANGPTL8 mRNA expression in portal hepatocytes and immature adipocytes. ANGPTL8 was expressed in the cells, which actively uptake and metabolize triglycerides. In hibernoma, the ANGPTL8 protein and mRNA were homogeneously expressed in tumor cells. The expression of ANGPTL8 was associated with the differentiation state and activity of lipid metabolism in a subpopulation of cells in the liver and adipose tissue. The association may be helpful for the understanding of local metabolic state in organs and diseases associated with the lipid metabolism.