Lipid Synthesis In Hepatocytes Research Articles

Qingluotongbi formula regulates the LXRα-ERS-SREBP-1c pathway in hepatocytes to alleviate the liver injury caused by Tripterygium wilfordii Hook. f.

Ethnopharmacological relevanceTripterygium wilfordii Hook. f. (TW) is widely used to treat autoimmune and inflammatory diseases; however, its development and application is limited by its significant association with liver injury. The compound formula Qingluotongbi (QLT) employs TW as its main component and is used to treat rheumatoid arthritis with no adverse reactions, suggesting that QLT may reduce the liver toxicity of TW. Aim of the studyWe examined whether TW interferes with lipid metabolism to induce liver injury, and evaluated the protective effect of QLT in in vivo and in vitro experiments. Materials and methodsAfter administration of QLT and its ingredients, HepaRG cells and SD rats were tested for biochemical indicators, hepatocytes lipid changes, and rat liver pathological changes, and then we analyzed for the gene expression of liver X receptor α (LXRα), endoplasmic reticulum stress (ERS) key proteins, sterol regulatory element binding protein-1c (SREBP-1c), and lipid-synthesizing enzymes. In HepaRG cells, the protein expression of glucose-regulated protein 78 kDa (GRP78) and LXRα was detected after addition of an LXRα inhibitor, LXRα agonist, and ERS inhibitor. ResultsTW caused significant elevation of biochemical indicators and lipid droplet deposition in hepatocytes, as well as upregulated the gene expression of LXRα, ERS key proteins, SREBP-1c, and lipid-synthesizing enzymes in both in vitro and in vivo settings, and caused liver injury in rats. QLT can alleviate the lipotoxic liver injury caused by TW. LXRα agonist further activated ERS induced by TW, whereas LXRα inhibitor significantly reduced ERS and lipotoxic injury induced by TW in HepaRG cells. ConclusionsTW upregulated LXRα to activate ERS and increased the gene expression of SREBP-1c and lipid-synthesizing enzymes, leading to increased lipid synthesis in hepatocytes to result in liver injury. QLT inhibited the LXRα-ERS-SREBP-1c pathway and reduced abnormal lipid synthesis in hepatocytes and the hepatotoxicity of TW.

Subcellular Distribution of Cholesterol and Sphingolipids in Rat Hepatocytes

Hepatocytes are central in energy and lipid homeostasis of mammals and as such are key players in maintaining and regulating serum cholesterol levels. In addition, hepatocytes produce bile, which has detergent properties and is the main product of cholesterol metabolism. The canalicular membrane is the site of bile formation and needs protective mechanisms against the detergent properties of bile. One such mechanism could be a specific lipid composition. We therefore aimed to use a targeted lipidomics approach to determine simultaneously the cholesterol and sphingolipid composition of the organelles involved in lipid synthesis in hepatocytes. Subcellular organelles were isolated from rat liver with standard methodologies and lipids were analyzed by either electrospray ionization mass spectrometry (glycerophospholipids and sphingolipids) or gas chromatography coupled mass spectrometry (sterols). Our data indicate that there is a distinct difference in cholesterol and sphingolipid content in the organelle fractions. Highest cholesterol content is found in basolateral plasma membranes and in the Golgi fraction, while endoplasmic reticulum displays a low cholesterol content. A high proportion of sphingomyelin is present in basolateral plasma membranes, smooth endoplasmic reticulum and in the Golgi apparatus. Ceramide content is higher in basolateral membranes compared to organelles and the canalicular plasma membrane. Glucosylceramide levels are very low and are mostly found in Golgi fractions. Our preliminary data so far show a parallel distribution of cholesterol and sphingolipids in subcellular fractions of rat hepatocytes.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Upregulation of miR-181a impairs hepatic glucose and lipid homeostasis.

The contributions of altered post-transcriptional gene silencing to the development of metabolic disorders remain poorly understood thus far. The objective of this study was to evaluate the roles of miR-181a in the regulation of hepatic glucose and lipid metabolism. MiR-181a is abundantly expressed in the liver, and we found that blood and hepatic miR-181a levels were significantly increased in patients and dairy cows with non-alcoholic fatty liver disease, as well as in high-fat diet and ob/ob mice. We determined that sirtuin1 is a target of miR-181a. Moreover, we found that hepatic sirtuin1 and peroxisome proliferator-activated receptor-γ coactivator-1α expression levels are downregulated, and acetylated peroxisome proliferator-activated receptor-γ coactivator-1α expression levels are upregulated in patients and dairy cows with non-alcoholic fatty liver disease, as well as in high-fat diet and ob/ob mice. MiR-181a overexpression inhibits the sirtuin1-peroxisome proliferator-activated receptor-γ coactivator-1α pathway, reduces insulin sensitivity, and increases gluconeogenesis and lipid synthesis in dairy cow hepatocytes and HepG2 cells. Conversely, silencing of miR-181a over-activates the sirtuin1-peroxisome proliferator-activated receptor-γ coactivator-1α pathway, increases insulin sensitivity and glycogen content, and decreases gluconeogenesis and lipid synthesis in hepatocytes, even under non-esterified fatty acids treatment conditions. Furthermore, miR-181a overexpression or sirtuin1 knockdown in mice increases lipid accumulation and decreases insulin sensitivity and glycogen content in the liver. Taken together, these findings indicate that increased hepatic miR-181a impairs glucose and lipid homeostasis by silencing sirtuin1 in non-alcoholic fatty liver disease.

Dyslipidemia and associated factors among diabetic patients attending Durame General Hospital in Southern Nations, Nationalities, and People's Region.

BackgroundDiabetes mellitus is a group of metabolic disorders that are caused by deficiency in insulin secretion or the decreased ability of insulin to act effectively on target tissues, particularly muscle, liver, and fat. As a result of insulin resistance in the target tissues, particularly in the adipocytes, free fatty acid flux is increased, leading to increased lipid synthesis in hepatocytes, which is responsible for diabetic dyslipidemia.ObjectiveThe objective of this study was to determine the prevalence and associated factors of dyslipidemia among diabetic patients in Durame General Hospital in Kembata Tembaro zone.MethodsA cross-sectional study was conducted from September 2015 to April 2016. In total, 224 subjects were involved in the study by using convenient sampling techniques. Face-to-face interview–administered questionnaire was used to collect sociodemographic data and other possible clinical data associated with the prevalence of dyslipidemia. Fasting venous blood specimens were collected to assess serum lipid profiles. Blood pressure (BP), weight, height, and waist circumference were measured.ResultsThe prevalence of dyslipidemia was 65.6%. Individual lipid abnormality of elevated LDL-C, TC, TG, and reduced HDL-C were identified in 43.8%, 23.7%, 40.6%, and 41.9% of study subjects, respectively. The prevalence of dyslipidemia was significantly associated with high BP, high body mass index, aging, and longer duration of diabetes mellitus.ConclusionHigh prevalence of dyslipidemia was found among diabetic patients in the study area. Therefore, a compressive mechanism is required to screen, treat, and prevent dyslipidemia.

Liver Clock Protein BMAL1 Promotes de Novo Lipogenesis through Insulin-mTORC2-AKT Signaling

The clock protein BMAL1 (brain and muscle Arnt-like protein 1) participates in circadian regulation of lipid metabolism, but its contribution to insulin AKT-regulated hepatic lipid synthesis is unclear. Here we used both Bmal1(-/-) and acute liver-specific Bmal1-depleted mice to study the role of BMAL1 in refeeding-induced de novo lipogenesis in the liver. Both global deficiency and acute hepatic depletion of Bmal1 reduced lipogenic gene expression in the liver upon refeeding. Conversely, Bmal1 overexpression in mouse liver by adenovirus was sufficient to elevate the levels of mRNA of lipogenic enzymes. Bmal1(-/-) primary mouse hepatocytes displayed decreased levels of de novo lipogenesis and lipogenic enzymes, supporting the notion that BMAL1 regulates lipid synthesis in hepatocytes in a cell-autonomous manner. Both refed mouse liver and insulin-treated primary mouse hepatocytes showed impaired AKT activation in the case of either Bmal1 deficiency or Bmal1 depletion by adenoviral shRNA. Restoring AKT activity by a constitutively active mutant of AKT nearly normalized de novo lipogenesis in Bmal1(-/-) hepatocytes. Finally, Bmal1 deficiency or knockdown decreased the protein abundance of RICTOR, the key component of the mTORC2 complex, without affecting the gene expression of key factors of insulin signaling. Thus, our study uncovered a novel metabolic function of hepatic BMAL1 that promotes de novo lipogenesis via the insulin-mTORC2-AKT signaling during refeeding.

Mechanism of Action of Compound-13: An α1-Selective Small Molecule Activator of AMPK

SummaryAMPK is a sensor of cellular energy status and a promising target for drugs aimed at metabolic disorders. We have studied the selectivity and mechanism of a recently described activator, C2, and its cell-permeable prodrug, C13. C2 was a potent allosteric activator of α1-complexes that, like AMP, also protected against Thr172 dephosphorylation. Compared with AMP, C2 caused only partial allosteric activation of α2-complexes and failed to protect them against dephosphorylation. We show that both effects could be fully restored by exchanging part of the linker between the autoinhibitory and C-terminal domains in α2, containing the equivalent region from α1 thought to interact with AMP bound in site 3 of the γ subunit. Consistent with our results in cell-free assays, C13 potently inhibited lipid synthesis in hepatocytes from wild-type and was largely ineffective in AMPK-knockout hepatocytes; its effects were more severely affected by knockout of α1 than of α2, β1, or β2.

Effects of High Zinc Levels on the Lipid Synthesis in Rat Hepatocytes

Zinc deficiency impairs the hepatic lipid metabolism. Previous studies were focused on the negative effects of zinc deficiency on the hepatic lipid metabolism. A few studies investigated the effects of high zinc levels on the lipid metabolism in hepatocytes. In this study, rat hepatocytes were cultured and treated with different and high concentrations of zinc to investigate the effects of high zinc levels on the lipid synthesis in hepatocytes in vitro. The levels of hepatocytes functional markers, including alkaline phosphatase, lactate dehydrogenase, and albumin, were significantly higher in the zinc treatment groups than in the control group (p < 0.05, p < 0.01). The mRNA and protein levels of sterol regulatory element-binding protein 1c (SREBP-1c) were significantly higher in the zinc treatment groups than in the control group (p < 0.05, p < 0.01). Furthermore, the mRNA expression levels of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS) were significantly higher in the medium- and high-dose zinc treatment groups than in the control group (p < 0.01). The mRNA levels of stearoyl-CoA desaturase-1 (SCD-1) were significantly higher in the high-dose group (p < 0.01). These results indicate that high levels of zinc increase hepatocytes activity and SREBP-1c expression, which upregulate the expression of ACC1, FAS, and SCD-1, thereby improving the lipid metabolism in the hepatocytes.

Non-Esterified Fatty Acids Activate the AMP-Activated Protein Kinase Signaling Pathway to Regulate Lipid Metabolism in Bovine Hepatocytes

Non-esterified fatty acids (NEFAs) act as signaling molecules involved in regulating genes expression to modulate lipid metabolism. However, the regulation mechanism of NEFAs on lipid metabolism in dairy cows is unclear. The AMP-activated protein kinase (AMPK) signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of NEFAs and AMPKα inhibitors (BML-275). NEFAs increased AMPKα phosphorylation through up-regulating the protein levels of liver kinase B1. Activated AMPKα increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α (PPARα). NEFAs also directly activate the PPARα independent of AMPKα. Activated PPARα increased the lipolytic genes expression to increase lipid oxidation. Furthermore, activated AMPKα inhibited the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid synthesis. Activated AMPKα phosphorylated and inhibited acetyl-CoA carboxylase and increased carnitine palmitoyltransferase-1 activity, which increased lipid oxidation. Consequently, the triglyceride content in the NEFAs-treated hepatocytes was significantly decreased. These results indicate that NEFAs activate the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in hepatocytes, which in turn, generates more ATP to relieve the negative energy balance in transition dairy cows.

801 Calcium-Dependent Signaling, via Calcineurin and NFAT, Is Key to Steatosis in Alcoholic Liver Disease (ALD) in Mice

Background: Alcohol abuse leads to alcoholic liver disease (ALD). In ALD hepatic steatosis is a prerequisite of disease progresses to steatohepatitis (SH) at which stage the liver injury becomes evident. The mechanisms of steatosis in ALD are noit fully understood. Calciumdependent signaling is activated in ALD in mice. The Aim of our study was to evaluate the role of calcium-dependent signaling in development of steatosis in ALD. Methods: We fed alcohol (Lieber-deCarli) or control diet to control C57Bl6 and NFAT-KO mice or cyclosporine-treated C57Bl6 mice. Results: Alcohol, but not control, diet led to significant ALD, revealed by elevated liver Tg content and significant OilRedO liver tissue staining suggestive of steatosis, increased serum ALT suggestive of liver injury, and serum cytokines TNFa, IL1, IL6, suggestive of inflammation, in C57Bl6 mice. There was significant elevation of calcium signaling in livers of alcohol-fed animals compared to control diet, as revealed by higher expression of Calcineurin, PLC, PKC, and MAPKp38 and elevated NFAT activity. Alcohol, but not control, diet lead to significant induction ACS, SCD1, ELOV16, GPAT and DGAT, LDLR HMG-CoA reductase mRNA in the livers of ethanol-fed animals. Further, the amount of mature SREBP-1protein, suggestive of SREBP activation, was increased in liver of alcoholfed animals. Inhibition of calcium signaling by either Cyclosporine treatment (at the level of Calcineurin) or by genetic NFAT deficiency partially prevented alcohol diet-induced upregulation of ACS, SCD1, ELOV16, GPAT and DGAT; more important, inhibition of calcium signaling led to partial protective against alcohol diet-induced liver injury and steatosis. NFAT protein was detected in both KCs and Hpt. In vitro, palmitic acid-exposed Hepa1.6 cells, used as surrogate of Hpt, developed steatosis; this process was significantly impaired when the cells were treated with cyclosporine and in cells made NFAT deficient by specific siRNA treatment. Co-culture of Hepa 1.6 cells+palmitic acid with inflammatory (LPS-pretreated) KCs lead to further upregulation of lipid uptake; sole exposure of KCs to cyclosporine did not prevent steatosis in co-culture. These data suggested that calciumdependent signaling mechanisms are involved in lipid synthesis in hepatocytes at different levels, including lipogenesis and lipolysis, in a KC-dependent manner. In conclusion, we report novel finding that calcium signaling is, in part, responsible for development of steatosis component of ALD in mice. It remains to be determined if inhibition of calcium signaling may be beneficial for delaying of steatosis and/or blunting of progression from HS to SH phases of ALD.

802 Tgfb Signaling Participates in Steatohepatitis Through the Induction of Cell Death and Suppression of Beta-Oxidation in Mice

Background: Alcohol abuse leads to alcoholic liver disease (ALD). In ALD hepatic steatosis is a prerequisite of disease progresses to steatohepatitis (SH) at which stage the liver injury becomes evident. The mechanisms of steatosis in ALD are noit fully understood. Calciumdependent signaling is activated in ALD in mice. The Aim of our study was to evaluate the role of calcium-dependent signaling in development of steatosis in ALD. Methods: We fed alcohol (Lieber-deCarli) or control diet to control C57Bl6 and NFAT-KO mice or cyclosporine-treated C57Bl6 mice. Results: Alcohol, but not control, diet led to significant ALD, revealed by elevated liver Tg content and significant OilRedO liver tissue staining suggestive of steatosis, increased serum ALT suggestive of liver injury, and serum cytokines TNFa, IL1, IL6, suggestive of inflammation, in C57Bl6 mice. There was significant elevation of calcium signaling in livers of alcohol-fed animals compared to control diet, as revealed by higher expression of Calcineurin, PLC, PKC, and MAPKp38 and elevated NFAT activity. Alcohol, but not control, diet lead to significant induction ACS, SCD1, ELOV16, GPAT and DGAT, LDLR HMG-CoA reductase mRNA in the livers of ethanol-fed animals. Further, the amount of mature SREBP-1protein, suggestive of SREBP activation, was increased in liver of alcoholfed animals. Inhibition of calcium signaling by either Cyclosporine treatment (at the level of Calcineurin) or by genetic NFAT deficiency partially prevented alcohol diet-induced upregulation of ACS, SCD1, ELOV16, GPAT and DGAT; more important, inhibition of calcium signaling led to partial protective against alcohol diet-induced liver injury and steatosis. NFAT protein was detected in both KCs and Hpt. In vitro, palmitic acid-exposed Hepa1.6 cells, used as surrogate of Hpt, developed steatosis; this process was significantly impaired when the cells were treated with cyclosporine and in cells made NFAT deficient by specific siRNA treatment. Co-culture of Hepa 1.6 cells+palmitic acid with inflammatory (LPS-pretreated) KCs lead to further upregulation of lipid uptake; sole exposure of KCs to cyclosporine did not prevent steatosis in co-culture. These data suggested that calciumdependent signaling mechanisms are involved in lipid synthesis in hepatocytes at different levels, including lipogenesis and lipolysis, in a KC-dependent manner. In conclusion, we report novel finding that calcium signaling is, in part, responsible for development of steatosis component of ALD in mice. It remains to be determined if inhibition of calcium signaling may be beneficial for delaying of steatosis and/or blunting of progression from HS to SH phases of ALD.

Akt Stimulates Hepatic SREBP1c and Lipogenesis through Parallel mTORC1-Dependent and Independent Pathways

Through unknown mechanisms, insulin activates the sterol regulatory element-binding protein (SREBP1c) transcription factor to promote hepatic lipogenesis. We find that this induction is dependent on the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). To further define the role of mTORC1 in the regulation of SREBP1c in the liver, we generated mice with liver-specific deletion of TSC1 (LTsc1KO), which results in insulin-independent activation of mTORC1. Surprisingly, the LTsc1KO mice are protected from age- and diet-induced hepatic steatosis and display hepatocyte-intrinsic defects in SREBP1c activation and de novo lipogenesis. These phenotypes result from attenuation of Akt signaling driven by mTORC1-dependent insulin resistance. Therefore, mTORC1 activation is not sufficient to stimulate hepatic SREBP1c in the absence of Akt signaling, revealing the existence of an additional downstream pathway also required for this induction. We provide evidence that this mTORC1-independent pathway involves Akt-mediated suppression of Insig2a, a liver-specific transcript encoding the SREBP1c inhibitor INSIG2.

The role of prolactin and progesterone in the regulation of lipogenesis in maternal and foetal rat liver in vivo and in isolated hepatocytes during the last day of gestation.

The administration of progesterone on day 21 of gestation increases the rates of lipogenesis in the liver in vivo and in hepatocytes isolated from rats on day 22 of pregnancy. Bromocriptine administration increases the rates of hepatic lipogenesis in vivo, but has no effect on lipid synthesis in hepatocytes under the same treatment conditions. Concurrently, the administration of progesterone or bromocriptine on day 21 to the mother increases the rates of lipogenesis in the foetal liver in vivo on day 22. The rates of lipid synthesis in foetal isolated hepatocytes are increased by progesterone administration, but remain unchanged by bromocriptine.

The regulation of lipid synthesis in freshly isolated and primary cultures of hepatocytes from fasted rats: The primary role of insulin

To determine the relative roles of insulin and intermediates in the glycolytic pathway in the control of lipogenesis, we have evaluated lipid synthesis in freshly isolated and primary cultures of hepatocytes from normal ad libitum fed and 72 hr fasted rats. In freshly isolated hepatocytes from fasted rats the rate of lipid synthesis is markedly depressed and resistant to the stimulatory effects of insulin and spermine, a post insulin binding mimicker of insulin action. This is true whether lipid synthesis is evaluated from 3H 2O or from ( 14C)-acetate. These characteristics are retained in primary cultures of these hepatocytes. This cell system, therefore, is suitable to evaluate the effects of insulin and substrates on the recovery of lipid synthesis in hepatocytes from fasted rats. Glucose, fructose, glycerol, pyruvate, and acetate in the incubation medium for 20 hr were without effect on the rate of lipid synthesis and insulin responsiveness in the primary cultures from fasted rats. However, when the cells were incubated for 20 hr with insulin, 10 −9 M, the rate of lipid synthesis and insulin responsiveness were comparable to that of primary cultures of hepatocytes from fed rats. The present studies demonstrate the unique role for insulin in restoring lipid synthesis and insulin responsiveness in mammalian liver from fasted animals.

Regulation of lipid synthesis in hepatocytes from lean and obese Zucker rats

Fatty acid synthesis and CO 2 production were evaluated in hepatocytes from lean and obese Zucker rats in the presence of 3H 2O, and several carbon precursors. The incorporation of 3H 2O into fatty acids was greater in obese compared to lean rats in both the isolated hepatocyte and in vivo. The rates of incorporation of 3H 2O into fatty acids and cholesterol in hepatocytes of both lean and obese rats were linear for 2 hr, in the absence or presence of 16.7 mM glucose. Rates of fatty acid synthesis were higher in the presence of 16.7 mM glucose compared to the absence of glucose in both lean and obese while rates of cholesterol synthesis were similar. The incorporation of 3H 2O into fatty acids, but not into cholesterol, was correlated with increasing glucose concentration and was 2 to three-fold higher in hepatocytes of obese compared to lean rats in the presence of several carbon precursors. Differences in CO 2 production between lean and obese rats suggested increased pentose phosphate shunt activity, decreased pyruvate dehydrogenase activity, and lower tricarboxylic acid cycle activity in obese rats. Fatty acid synthesis and CO 2 production from 3H 2O and [U- 14C]glucose in hepatocytes of lean and obese rats was similarly elevated by insulin and depressed by glucagon at several concentrations, suggesting that hepatocytes of obese animals respond to these hormones. These data indicate that rates of hepatic fatty acid synthesis although higher in obese rats respond to modulation in a fashion which is similar to the response in lean rats. The present studies suggest that the oxidation of several carbon precursors in the tricarboxylic acid cycle is diminished in obese compared to lean rats, but pentose phosphate shunt activity is greater in the obese Zucker rats.

Lipid synthesis in isolated intestinal cells.

Since the small intestine contributes significantly to serum cholesterol and very low density lipoprotein levels, acute regulation of lipid synthesis was investigated in isolated rat intestinal cells incubated in Krebs-Ringer bicarbonate buffer with 5 mM glucose and [14c]acetate or 3H2O. Incorporation of [14c]acetate into cellular lipids was 6- to 8-fold greater in crypt than in villus cells. In both cell types the distribution of 14C among the various lipid classes was as follows: 52.5% in triglycerides, diglycerides, and monoglycerides; 22.3% in cholesterol; 8.3% in cholesteryl esters; 1.9% in fatty acids; and 15.0% in phospholidpids. In contrast, the medium lipids contained significantly higher amounts of tri-, di- and monoglycerides (61.1%) and lower amounts of cholesteryl esters (2.3%) and phospholipids (11.9%). After saponification, 2/3 of the recovered 3H2O was in fatty acids and 1/3 in cholesterol. Ethanol (10 mM) tripled 3H2O incorporation into cellular lipids but had no effect on [14c]acetate incorporation. Epinephrine and norepinephrine (10 micron), glucagon (10 micron), dibutyryl cyclic AMP (1MM), dexamethasone (1 mM and 1 micron), and cholera toxin (1 microgram/ml) did not affect [14c]acetate incorporation. We concluded that ehtanol stimulates intestinal lipid synthesis; however, in sharp contrast to their inhibition of lipid synthesis in hepatocytes and adipocytes, catecholamines, glucagon, and dibutyryl cyclic AMP do not inhibit lipid synthesis in intestinal cells.

Species differences in the hormonal control of lipogenesis in rat and chicken hepatocytes

Abstract 1. 1. Suspensions of hepatocytes were prepared under the same conditions by in situ perfusion of rat or chicken livers with an enzyme solution for comparative metabolic studies. 2. 2. Isolated cells from either species incorporated 14 C-acetate into cellular lipids, but the rate of lipogenesis was more rapid in chicken hepatocytes. 3. 3. Dibutyryl cyclic AMP (0·1 mM) inhibited lipid synthesis in hepatocytes from either species, but its effect was far greater in chicken hepatocytes. Cyclic AMP (0·1 mM) had no effect on lipogenesis in rat hepatocytes while its effect on this process in chicken hepatocytes was similar to that of the dibutyryl derivative. 4. 4. Epinephrine and glucagon were antilipogenic in cells from both species, but each hormone had a more potent inhibitory effect in chicken hepatocytes. In each species, the effect of glucagon was greater than that of epinephrine.