Porcine G0/G1 Switch Gene 2 (G0S2) Expression is Regulated During Adipogenesis and Short-Term In-Vivo Nutritional Interventions

Adipose triglyceride lipase (ATGL), catalyzing the initial step of hydrolysis of triacylglycerol (TAG) in adipocytes, has been known to be inhibited by G0/G1 switch gene 2 (G0S2). In this study, we report the porcine G0S2 cDNA and amino acid sequences as well as the expression level of porcine G0S2. The porcine G0S2 mRNA was abundantly expressed in adipose tissue and liver among various tissues. In adipose tissue, porcine G0S2 expression was 16-fold higher in the fat cell fraction than the stromal vascular fraction. The G0S2 level increased significantly during adipogenesis in vitro and in vivo. These data indicate that G0S2 expression is closely associated with lipid accumulation and adipogenesis. Considering G0S2 as an inhibitor of cell proliferation, the relatively low levels of G0S2 in preadipocytes and adipose tissues of fetal and neonatal pigs compared to adipocytes and adipose tissues of adult pigs may allow the fast cell proliferation rates. Further studies showed that a short-term 24-h fast down-regulated G0S2 expression and increased ATGL expression in adipose tissue; however, a long-term calorie restriction for 8 days had no influence on the level of G0S2 but increased ATGL expression. Therefore, porcine G0S2, which is both a negative regulator of ATGL-mediated lipolysis and cell proliferation in adipose tissue, can be down-regulated in vivo by a short-term 24-h fast followed by increased ATGL-mediated lipolysis.     

Bovine Adipose Triglyceride Lipase is Not Altered and Adipocyte Fatty Acid-Binding Protein is Increased by Dietary Flaxseed

In this paper, we report the full-length coding sequence of bovine ATGL cDNA and analyze its expression in bovine tissues. Similar to human, mouse, and pig ATGL sequences, bovine ATGL has a highly conserved patatin domain that is necessary for lipolytic function in mice and humans. This suggests that ATGL is functionally intact as a triglyceride lipase in cattle. Tissue distribution of ATGL gene expression was highest in fat and muscle (skeletal and cardiac) tissue, while protein expression was solely detectible in the adipose tissue. The effect of 109 days of flaxseed supplementation on ATGL and adipocyte fatty acid-binding protein (FABP4 or A-FABP, E-FABP or FABP5) expression was examined in Angus steers. Supplemented steers had greater triacylglycerol (TAG) content in the muscle compared with unsupplemented ones. Additionally, supplementation increased A-FABP expression and decreased stearoyl-CoA desaturase 1 (SCD-1) expression in muscle, while total ATGL expression was unaffected. In summary, supplementation of cattle rations with flaxseed increased muscle TAG concentrations attributed in part to increased expression of key enzymes involved in lipid trafficking (A-FABP) and metabolism (SCD-1).     

β<Subscript>3</Subscript>-Adrenergic Signaling Acutely Down Regulates Adipose Triglyceride Lipase in Brown Adipocytes

Mice exposed to cold rely upon brown adipose tissue (BAT)-mediated nonshivering thermogenesis to generate body heat using dietary glucose and lipids from the liver and white adipose tissue. In this report, we investigate how cold exposure affects the PI3 K/Akt signaling cascade and the expression of genes involved in lipid metabolism and trafficking in BAT. Cold exposure at an early time point led to the activation of the PI3 K/Akt, insulin-like signaling cascade followed by a transient decrease in adipose triglyceride lipase (ATGL) gene and protein expression in BAT. To further investigate how cold exposure-induced signaling altered ATGL expression, cultured primary brown adipocytes were treated with the β₃-adrenergic receptor (β₃AR) agonist CL 316,243 (CL) resulting in activation of PI3 K/Akt, ERK 1/2, and p38 signaling pathways and significantly decreased ATGL protein levels. ATGL protein levels decreased significantly 30 min post CL treatment suggesting protein degradation. Inhibition of PKA signaling by H89 rescued ATGL levels. The effects of PKA signaling on ATGL were shown to be independent of relevant pathways downstream of PKA such as PI3 K/Akt, ERK 1/2, and p38. However, CL treatment in 3T3-L1 adipocytes did not decrease ATGL protein and mRNA expression, suggesting a distinct response in WAT to β3-adrenergic agonism. Transitory effects, possibly attributed to acute Akt activation during the early recruitment phase, were noted as well as stable changes in gene expression which may be attributed to β3-adrenergic signaling in BAT.     

Loss of Fat with Increased Adipose Triglyceride Lipase-Mediated Lipolysis in Adipose Tissue During Laying Stages in Quail

The goal of the current study was to investigate regulation of key genes involved in lipid metabolism in adipose and liver to relate lipolytic and lipogenic capacities with physiological changes at the pre-laying, onset of laying, and actively laying stages of quail. Followed by a 50 % increase from pre-laying to onset of laying, adipose to body weight ratio was significantly reduced by 60 % from the onset of laying to the actively laying stage (P < 0.05), mainly resulting from the significantly increased adipocyte size from the pre-laying stage to the onset of laying and reduction of adipocyte size from the onset of laying to the actively laying stage (P < 0.05). In the adipose tissue of actively laying quail, increased protein expression and phosphorylation of adipose triglyceride lipase (ATGL) together with an elevated mRNA expression of comparative gene identification-58, an activator of ATGL, contributes to increased lipolytic activity, as proved by increased amounts of plasma non-esterified fatty acid (P < 0.05). In addition, decreased mRNA expression of fatty acid transport protein in the actively laying quail could contribute to the adipocyte hypotrophy (P < 0.05). In the liver, relative mRNA expression of apo-very low density lipoprotein (VLDL)-II increased significantly from the pre-laying to actively laying stages (P < 0.05), indicating increased apoVLDL-II actively facilitated VLDL secretion in the actively laying quail. These results suggest that the laying birds undergo active lipolysis in the adipocyte, and increase VLDL secretion from the liver in order to secure a lipid supply for yolk maturation.     

In Vitro TNF-α- and Noradrenaline-Stimulated Lipolysis is Impaired in Adipocytes from Growing Rats Fed a Low-Protein, High-Carbohydrate Diet

The aim of this study was to investigate tumor necrosis factor alpha (TNF-α)- and noradrenaline (NE)-stimulated lipolysis in retroperitoneal (RWAT) and epididymal (EAT) white adipose tissue as a means of understanding how low-protein, high-carbohydrate (LPHC) diet-fed rats maintain their lipid storage in a catabolic environment (marked by increases in serum TNF-α and corticosterone and sympathetic flux to RWAT and EAT), as previously observed. Adipocytes or tissues from the RWAT and EAT of rats fed an LPHC diet and rats fed a control (C) diet for 15 days were used in the experiments. The adipocytes from both tissues of the LPHC rats exhibited lower TNF-α- stimulated lipolysis compared to adipocytes from the C rats. The intracellular lipolytic agents IBMX, DBcAMPc and FSK increased lipolysis in both tissues from rats fed the C and LPHC diets compared to basal lipolysis; however, the effect was approximately 2.5-fold lower in adipocytes from LPHC rats. The LPHC diet induced a marked reduction in the β₃ and α₂-AR, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) content in RWAT and EAT. The LPHC diet did not affect TNF-α receptor 1 content but did induce a reduction in ERK p44/42 in both tissues. The present work indicates that RWAT and EAT from LPHC rats have an impairment in the lipolysis signaling pathway activated by NE and TNF-α, and this impairment explains the reduced response to these lipolytic stimuli, which may be fundamental to the maintenance of lipid storage in LPHC rats.     

Acute Up-Regulation of Adipose Triglyceride Lipase and Release of Non-Esterified Fatty Acids by Dexamethasone in Chicken Adipose Tissue

The mechanism of adipose tissue lipolysis has not been fully elucidated. Greater understanding of this process could allow for increased feed efficiency and reduced fat in poultry. Studies in avian species may provide important insight in developing therapies for human obesity, as lipolytic pathways are highly conserved. Adipose triglyceride lipase (ATGL) cleaves triacylglycols, releasing non-esterified fatty acids (NEFA) into the bloodstream. Glucocorticoids have been shown to elevate circulating NEFA. To determine the regulation of ATGL and regulator proteins comparative gene identification-58 (CGI-58) and G(0)/G(1) switch gene 2 (G0S2) by glucocorticoid, 36 chickens received an injection of dexamethasone (4 mg/kg). Saline was administered to an additional 12 birds to determine any effect of stress during handling. Dexamethasone-injected birds were harvested at 0, 0.5, 1, 2, 4, and 6 h after treatment; saline-treated birds were collected at 4 and 6 h. Abdominal and subcutaneous adipose tissue and blood were collected. Gene and protein expression were analyzed via quantitative real-time PCR and western blot. Compared with the saline group, ATGL expression increased in birds injected with dexamethasone. When dexamethasone response was compared to the untreated group up to 6 h following injection, an increase in ATGL protein was observed as quickly as 0.5 h and increased further from 1 to 6 h. Plasma NEFA and glucose increased gradually from 0 to 6 h, reaching statistical significance at 4 h. These data show that ATGL expression is stimulated by glucocorticoid in a time-dependent manner.     

Micro RNA-124a Regulates Lipolysis via Adipose Triglyceride Lipase and Comparative Gene Identification 58

Lipolysis is the biochemical pathway responsible for the catabolism of cellular triacylglycerol (TG). Lipolytic TG breakdown is a central metabolic process leading to the generation of free fatty acids (FA) and glycerol, thereby regulating lipid, as well as energy homeostasis. The precise tuning of lipolysis is imperative to prevent lipotoxicity, obesity, diabetes and other related metabolic disorders. Here, we present our finding that miR-124a attenuates RNA and protein expression of the major TG hydrolase, adipose triglyceride lipase (ATGL/PNPLA2) and its co-activator comparative gene identification 58 (CGI-58/ABHD5). Ectopic expression of miR-124a in adipocytes leads to reduced lipolysis and increased cellular TG accumulation. This phenotype, however, can be rescued by overexpression of truncated Atgl lacking its 3''UTR, which harbors the identified miR-124a target site. In addition, we observe a strong negative correlation between miR-124a and Atgl expression in various murine tissues. Moreover, miR-124a regulates the expression of Atgl and Cgi-58 in murine white adipose tissue during fasting as well as the expression of Atgl in murine liver, during fasting and re-feeding. Together, these results point to an instrumental role of miR-124a in the regulation of TG catabolism. Therefore, we suggest that miR-124a may be involved in the regulation of several cellular and organismal metabolic parameters, including lipid storage and plasma FA concentration.     

Modulation of cutaneous fatty acid-binding protein mRNA expression in rat adipose tissues by hereditary obesity and dietary fats

Cutaneous fatty acid-binding protein (C-FABP) is a member of the intracellular lipid-binding protein multigene family expressed in various tissues. A high level of C-FABP mRNA in adipose tissue has been reported, but its physiological significance in regulating adipose tissue function is not clear. To obtain insights into the role of C-FABP in adipose tissue, we studied the obesity-related and dietary fat-related changes of C-FABP mRNA expression in adipose tissues. C-FABP mRNA levels in interscapular brown adipose tissue, and epididymal and perirenal white adipose tissues were higher in Zucker fatty rats than in lean controls despite that the difference in brown adipose tissue was not significant. Fish oil compared to palm and safflower oils significantly reduced the mRNA level of C-FABP in brown adipose tissue and epididymal and perirenal white adipose tissues in Sprague-Dawley rats except for one occasion. Our study demonstrated that C-FABP is a protein whose mRNA expression is easily modified by hereditary obesity and the type of dietary fat. Therefore, C-FABP may play a significant role in regulating adipocyte function in response to changes in nutritional conditions.     

Alpha-Lipoic Acid Alleviates Acute Inflammation and Promotes Lipid Mobilization During the Inflammatory Response in White Adipose Tissue of Mice

Recently, white adipose tissue has been shown to exhibit immunological activity, and may play an important role in host defense and protection against bacterial infection. Αlpha‐lipoic acid (α‐LA) has been demonstrated to function as an anti‐inflammatory and anti‐oxidant agent. However, its influence on the inflammatory response and metabolic changes in white adipose tissue remains unknown. We used male C57BL/6 mice as models to study the effect of α‐LA on the inflammatory response and metabolic changes in white adipose tissue after stimulation with lipopolysaccharide (LPS). The non‐esterified fatty acid content was measured by an automatic biochemical analyzer. The expression of inflammation‐, lipid‐ and energy metabolism‐related genes and proteins was determined by quantitative real‐time polymerase chain reaction and western blotting. The results indicated that α‐LA significantly decreased the epididymis fat weight index and the non‐esterified fatty acid content in plasma compared with the control group. LPS significantly increased the expression of inflammation genes and α‐LA reduced their expression. The LPS‐induced expression of nuclear factor‐κB protein was decreased by α‐LA. Regarding lipid metabolism, α‐LA significantly counteracted the inhibitory effects of LPS on the expression of hormone‐sensitive lipase gene and protein. α‐LA evidently increased the gene expression of fatty acid transport protein 1 and cluster of differentiation 36. Regarding energy metabolism, α‐LA significantly increased the expression of most of mitochondrial DNA‐encoded genes compared with the control and LPS group. Accordingly, α‐LA can alleviate acute inflammatory response and this action may be related with the promotion of lipid mobilization in white adipose tissue.     

Overexpression of G0/G1 Switch Gene 2 in Adipose Tissue of Transgenic Quail Inhibits Lipolysis Associated with Egg Laying

In avians, yolk synthesis is regulated by incorporation of portomicrons from the diet, transport of lipoproteins from the liver, and release of lipids from adipose tissue; however, the extent to which lipolysis in adipose tissue contributes to yolk synthesis and egg production has yet to be elucidated. G0/G1 switch gene 2 (G0S2) is known to bind and inhibit adipose triglyceride lipase (ATGL), the rate-limiting enzyme in lipolysis. The objective of this study was to determine whether overexpression of the G0S2 gene in adipose tissue could successfully inhibit endogenous ATGL activity associated with egg laying. Two independent lines of transgenic quail overexpressing G0S2 had delayed onset of egg production and reduced number of eggs over a six-week period compared to non-transgenic quail. Although no differences in measured parameters were observed at the pre-laying stage (5 weeks of age), G0S2 transgenic quail had significantly larger interclavicular fat pad weights and adipocyte sizes and lower NEFA concentrations in the serum at early (1 week after laying first egg) and active laying (5 weeks after laying first egg) stages. Overexpression of G0S2 inhibited lipolysis during early and active laying, which drastically shifted the balance towards a net accumulation of triacylglycerols and increased adipose tissue mass. Thereby, egg production was negatively affected as less triacylglycerols were catabolized to produce lipids for the yolk.     

Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice

Adult humans and mice possess significant classical brown adipose tissues (BAT) and, upon cold-induction, acquire brown-like adipocytes in certain depots of white adipose tissues (WAT), known as beige adipose tissues or WAT browning/beiging. Activating thermogenic classical BAT or WAT beiging to generate heat limits diet-induced obesity or type-2 diabetes in mice. Adiponectin is a beneficial adipokine resisting diabetes, and causing “healthy obese” by increasing WAT expansion to limit lipotoxicity in other metabolic tissues during high-fat feeding. However, the role of its receptors, especially adiponectin receptor 1 (AdipoR1), on cold-induced thermogenesis in vivo in BAT and in WAT beiging is still elusive. Here, we established a cold-induction procedure in transgenic mice over-expressing AdipoR1 and applied a live 3-D [¹⁸F] fluorodeoxyglucose-PET/CT (¹⁸F-FDG PET/CT) scanning to measure BAT activity by determining glucose uptake in cold-acclimated transgenic mice. Results showed that cold-acclimated mice over-expressing AdipoR1 had diminished cold-induced glucose uptake, enlarged adipocyte size in BAT and in browned WAT, and reduced surface BAT/body temperature in vivo. Furthermore, decreased gene expression, related to thermogenic Ucp1, BAT-specific markers, BAT-enriched mitochondrial markers, lipolysis and fatty acid oxidation, and increased expression of whitening genes in BAT or in browned subcutaneous inguinal WAT of AdipoR1 mice are congruent with results of PET/CT scanning and surface body temperature in vivo. Moreover, differentiated brown-like beige adipocytes isolated from pre-adipocytes in subcutaneous WAT of transgenic AdipoR1 mice also had similar effects of lowered expression of thermogenic Ucp1, BAT selective markers, and BAT mitochondrial markers. Therefore, this study combines in vitro and in vivo results with live 3-D scanning and reveals one of the many facets of the adiponectin receptors in regulating energy homeostasis, especially in the involvement of cold-induced thermogenesis.     

Effects of dietary conjugated linoleic acid on the expression of uncoupling proteins in mice and rats

CLA inhibits mammary cancer and reduces body fat accumulation in rodents. It is not known whether uncoupling proteins (UCP), which are modulators of energy balance and metabolism, play a role in these actions of CLA. To determine the effects of dietary CLA on the expression of UCP in various tissues, 5-wk-old Sprague-Dawley rats and C57BI/6 mice were fed diets containing 1% CLA for 3 wk. CLA treatment reduced adipose depot weights in both rats and mice but had no significant effects on body weight. There was a species-specific effect of CLA on the expression of UCP. Whereas CLA did not affect the expression of UCP in most tissues in rats, mice fed CLA had increased expression of UCP2 in the mammary gland, brown adipose tissue (BAT), and white adipose tissue (WAT). Furthermore, UCP1 and UCP3 mRNA and protein levels in BAT were significantly lower in CLA-fed mice compared to controls. Skeletal muscle UCP3 mRNA was unchanged, but UCP3 protein levels were significantly increased in mice, suggesting translational or posttranslational regulation of this protein. Results from this study suggest that alterations in the expression of UCP in mice may be related to the previously reported effects of dietary CLA in lowering adiposity and increasing FA oxidation. In rats, however, induction of UCP is not likely to be responsible for fat reduction or for the inhibitory action of CLA on mammary carcinogenesis.     

Cold-Induced Browning Dynamically Alters the Expression Profiles of Inflammatory Adipokines with Tissue Specificity in Mice

Cold exposure or β₃-adrenoceptor agonist treatment induces the adipose tissues remodeling, relevant for beige adipogenesis within white adipose tissue (WAT). It remains unclear whether this process influences inflammatory adipokines expression in adipose tissues. We determine the temporal profile of cold or β₃-adrenoceptor agonist (CL316,243)-induced changes in the expression of inflammatory adipokines in adipose tissues in mice or primary mice adipocytes. Male C57BL/6J mice at eight weeks old were exposed to 4 °C for 1–5 days. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous WAT (sWAT) and epididymal WAT (eWAT) were harvested for gene and protein expression analysis. In addition, cultured primary mice brown adipocyte (BA) and white adipocyte (WA) treated with or without CL316,243 were harvested for gene expression analysis. The inflammatory adipokines expressed significantly higher in WAT than BAT at baseline. They were rapidly changed in iBAT, while down-regulated in sWAT and up-regulated in eWAT during the cold acclimation. Upon CL316,243 treatment, detected inflammatory adipokines except Leptin were transiently increased in both BA and WA. Our in vivo and in vitro data demonstrate that the browning process alters the inflammatory adipokines expression in adipose tissues, which is acutely responded to in iBAT, dynamically decreased in sWAT whilst increased in eWAT for compensation.     

Phenotypic Characterization of Transgenic Mice Expressing Human IGFBP-5

Pulmonary fibrosis is one of the important causes of morbidity and mortality in fibroproliferative disorders such as systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Insulin-like growth factor binding protein-5 (IGFBP-5) is a conserved member of the IGFBP family of proteins that is overexpressed in SSc and IPF lung tissues. In this study, we investigated the functional role of IGFBP-5 in the development of fibrosis in vivo using a transgenic model. We generated transgenic mice ubiquitously expressing human IGFBP-5 using CRISPR/Cas9 knock-in. Our data show that the heterozygous and homozygous mice are viable and express human IGFBP-5 (hIGFBP-5). Transgenic mice had increased expression of extracellular matrix (ECM) genes, especially Col3a1, Fn, and Lox in lung and skin tissues of mice expressing higher transgene levels. Histologic analysis of the skin tissues showed increased dermal thickness, and the lung histology showed subtle changes in the heterozygous and homozygous mice as compared with the wild-type mice. These changes were more pronounced in animals expressing higher levels of hIGFBP-5. Bleomycin increased ECM gene expression in wild-type mice and accentuated an increase in ECM gene expression in transgenic mice, suggesting that transgene expression exacerbated bleomycin-induced pulmonary fibrosis. Primary lung fibroblasts cultured from lung tissues of homozygous transgenic mice showed significant increases in ECM gene expression and protein levels, further supporting the observation that IGFBP-5 resulted in a fibrotic phenotype in fibroblasts. In summary, transgenic mice expressing human IGFBP-5 could serve as a useful animal model for examining the function of IGFBP-5 in vivo.     

Hepatic and Adipose Tissue Depot-Specific Changes in Lipid Metabolism in Late-Onset Obese (LOB) Rats

Transgenic Late-onset OBesity (LOB) rats slowly develop a male-specific, autosomal dominant, obesity phenotype with a specific increase in peri-renal white adipose tissue (WAT) depot and preserved insulin sensitivity (Bains et al. in Endocrinology 145:2666–2679, 2004). To better understand the remarkable phenotype of these rats, the lipid metabolism was investigated in male LOB and non-transgenic (NT) littermates. Total plasma cholesterol (C) levels were normal but total plasma triacylglycerol (TAG) (2.8-fold) and hepatic TAG content (25%) was elevated in LOB males. Plasma VLDL-C and VLDL-TAG levels were higher while plasma apoB levels were 60% lower in LOB males. Increased hepatic TAG secretion explained the increased VLDL levels in LOB males. The hepatic gene expression of FAS, SCD-1, mitochondrial (mt)GPAT, and DGAT2 was up-regulated in both old obese and young non-obese LOB rats. Lipoprotein lipase (LPL) activity in heart and epididymal white adipose tissue (WAT) was unchanged, while LPL activity was increased in peri-renal WAT (30%) and decreased in soleus muscle (40%). Moreover, FAS, SCD-1 and DGAT2 gene expression was increased in peri-renal, but not in epididymal WAT. Basal lipolysis was reduced or unchanged and β-adrenergic stimulated lipolysis was reduced in WAT from both old obese and young non-obese LOB rats. To summarize, the obese phenotype of LOB male rats is associated with increased hepatic TAG production and secretion, a shift in LPL activity from skeletal muscle to WAT, reduced lipolytic response in WAT depots and a specific increase in expression of genes responsible for fatty acid and TAG synthesis in the peri-renal depot. F. Frick and R. Hume contributed equally to this work.     

P2Y2R Deficiency Ameliorates Hepatic Steatosis by Reducing Lipogenesis and Enhancing Fatty Acid β-Oxidation through AMPK and PGC-1α Induction in High-Fat Diet-Fed Mice

Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease associated with obesity and insulin resistance. Activation of the purinergic receptor P2Y2R has been reported to promote adipogenesis, inflammation and dyslipidemia in adipose tissues in obese mice. However, the role of P2Y2R and its mechanisms in NAFLD remain unknown. We hypothesized that P2Y2R deficiency may play a protective role in NAFLD by modulating lipid metabolism in the liver. In this study, we fed wild type and P2Y2R knockout mice with a high-fat diet (HFD) for 12 weeks and analyzed metabolic phenotypes. First, P2Y2R deficiency effectively improved insulin resistance with a reduction in body weight and plasma insulin. Second, P2Y2R deficiency attenuated hepatic lipid accumulation and injury with reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Third, P2Y2R deficiency decreased the expression of fatty acid synthesis mediators (cluster of differentiation (CD36), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD1)); and increased the expression of adipose triglyceride lipase (ATGL), a lipolytic enzyme. Mechanistically, P2Y2R deficiency increased the AMP-activated protein kinase (AMPK) activity to improve mitochondrial fatty acid β-oxidation (FAO) by regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1A (CPT1A)-mediated FAO pathway. In addition, P2Y2R deficiency increased peroxisome proliferator-activated gamma co-activator-1α (PGC-1α)-mediated mitochondrial biogenesis. Conclusively, P2Y2R deficiency ameliorated HFD-induced hepatic steatosis by enhancing FAO through AMPK signaling and PGC-1α pathway, suggesting P2Y2R as a promising therapeutic target for NAFLD.     

Differential effects of obesity on acetoacetyl‐CoA synthetase gene in rat adipose tissues

In order to investigate the physiological role of the ketone body‐utilizing enzyme acetoacetyl‐CoA synthetase (AACS) in obesity‐induced metabolic derangements, we examined the mRNA levels of AACS and other lipogenic enzymes in white adipose tissues (WAT) in the different types of obesity, genetic (Zucker fatty) and high‐fat diet (HFD)‐induced obesity. Plasma ketone body levels and gene expression levels of AACS and acetyl‐CoA carboxylase‐2 (ACC‐2) in WAT were lower in Zucker fatty rats than in lean rats. On the contrary, in HFD‐induced obese rats, these levels were increased. Moreover, AACS mRNA expression was affected only in subcutaneous WAT by each type of obesity. Our data suggest that AACS mRNA expression is related to obesity‐induced alteration of plasma ketone body levels, and that AACS in subcutaneous WAT plays an important role in the regulation of lipogenesis and ketone body utilization in various obese conditions.     

Parenteral Lipid Emulsions in Guinea Pigs Differentially Influence Plasma and Tissue Levels of Fatty Acids,Squalene, Cholesterol,and Phytosterols

Lipid emulsions are made by mixing vegetable and/or fish oils with egg yolk and contain different types and amounts of fatty acids and sterols. This study assessed the effects of oral diet, soybean oil (SO)-, fish oil (FO)-, a mixture of olive and soybean oil (OOSO)-, and a mixture of fish, olive, coconut, and soybean oil (FOCS)-based emulsions on plasma triacylglycerols and plasma and tissue fatty acid and sterol content following acute and chronic intravenous administration in the guinea pig. Upon acute administration, peak triacylglycerols were highest with SO and lowest with OOSO. Upon chronic administration, the plasma triglyceride levels did not increase in any group over that of the controls. Fatty acid levels varied greatly between organs of animals on the control diets and organs of animals following acute or chronic lipid administration. Squalene levels increased in plasma following acute administration of OOSO, but plasma squalene levels were similar to control in all emulsion groups following chronic administration. Total plasma phytosterol levels were increased in the SO, OOSO, and FOCS groups following both acute and chronic infusions, whereas phytosterols were not increased following FO infusion. Total phytosterol levels were higher in liver, lung, kidney and adipose tissue following SO and OOSO. Levels were not increased in tissues after FO and FOCS infusion. These results indicate that fatty acid and sterol contents vary greatly among organs and that no one tissue reflects the fatty acid or sterol composition of other tissues, suggesting that different organs regulate these compounds differently.