β-Oxidation capacity in liver increases during parr-smolt transformation of Atlantic salmon fed vegetable oil and fish oil

Atlantic salmon Salmo salar were fed diets containing 100% fish oil (FO; capelin oil) or 100% vegetable oil (VO) from start of feeding until the fish reached the size of 2·5 kg. Samples were taken during the period of the parr-smolt transformation (October 2002 to February 2003). The VO diet consisted of a blend of 55% rapeseed oil, 30% palm oil and 15% linseed oil to maintain the sum of saturated, monounsaturated and polyunsaturated fatty acids between the two diets, although with differences in the individual chain length of fatty acids. Na⁺/K⁺-ATPase activity in the gills, total β-oxidation capacity in muscles and liver and total lipid, glycogen and dry matter content in the muscles were measured during the parr-smolt transformation and after seawater transfer. Na⁺/K⁺-ATPase activity in gills increased prior to seawater transfer, showing an adaptation for seawater survival. Major changes in the lipid and glycogen content in the fillet and in β-oxidation capacity were found in the tissues measured. β-oxidation capacity increased significantly in liver and decreased in red muscle, prior to seawater transfer, giving liver an important role in energy production during this period. Results also indicated that feeding Atlantic salmon a diet where 100% of FO was replaced with VO did not have any negative effects on lipid metabolism during parr-smolt transformation.     

Seasonal variations in the lipid composition of the steelhead trout, Salmo gairdneri Richardson, associated with the parr-smolt transformation

Total lipid and lipid class composition of selected tissues and serum were determined for juvenile steelhead trout Salmo gairdneri , during the smolting period between 25 January and 19 April 1982. The total lipid content of the serum, liver, light muscle and dark muscle was significantly depleted during smolt transformation. Mesenteric fat total lipid concentration fluctuated little over the sampling period. Phospholipids of muscle and mesenteric fat exhibited little seasonality. Cholesterol was significantly depleted from dark muscle and liver. Large stores of triacylglycerol (TGL) in the parrs' mesenteric fat, dark muscle and liver implicate these tissues as lipid depot organs. In those tissues depleted of lipid, TGL concentrations were reduced more than any other lipid class. This supports the hypothesis that increased catabolism is the cause of loss of body fat during salmonid smolt transformation.     

Diurnal variations in the physiology of the goldfish,Carassius auratus

Abstract

Liver glycogen, liver lipid, liver triglycerides, plasma glucose, plasma total lipid, plasma cholesterol, plasma corticoids, hypothalamic serotonin and pituitary pro‐lactin levels were assayed at five times over a 24‐h period in Carassius auratus maintained under a specific photoperiod regime at various times throughout the year. Diurnal variations were observed in all parameters monitored. Daily variations of liver glycogen, plasma glucose, plasma lipid, plasma corticoids and hypothalamic serotonin were affected by time of feeding. Liver glycogen, plasma lipid and plasma corticoid levels were also affected by time of feeding. Diurnal variations of liver glycogen, plasma glucose and plasma lipid were influenced by light‐dark cycles. These data illustrate that feeding time, photoperiod and time of sacrifice are important considerations in the study of metabolic and hormonal parameters in fishes.     

中华蟾蜍糖原含量的季节变化

于2005年11月至2006年10月,用硫酸-蒽酮比色法和比重法测定了中华蟾蜍各月份的肝糖原和肌糖原含量及肝比重。结果显示:冬眠期间(11月至次年的2月),糖原含量逐月下降;2月份时出现临时回升,然后继续下降;4月份时肝糖原含量最低;5月份起,肝糖原含量逐渐上升;5月份时肌糖原含量为最低;6月份起,肌糖原含量逐渐上升。虽然在7-8月间出现过下降,两种糖原的含量在10月份时达到一年中的最高值。这些结果表明,蟾蜍糖原含量在一年中呈现显著的季节性波动。越冬前所储备糖原的一部分可能用于越冬期间维持高水平的血糖,一部分用于基础代谢。2月份时糖原含量的临时上升,可能是血液中作为防冻保护剂的葡萄糖运回肝脏和肌肉中再合成糖原的结果。7-8月间糖原含量降低可能与蟾蜍夏蛰有关。雌性5月至10月期间的肝糖原总体水平显著低于雄性,可能与依赖可得到葡萄糖的卵母细胞中的糖原合成有关。糖原含量的季节变化与蟾蜍的生活状态(越冬、繁殖等)有关,并与血糖含量有联动关系。     

Effect of dietary conjugated linoleic acid (CLA) on lipid composition, metabolism and gene expression in Atlantic salmon (Salmo salar) tissues

Dietary conjugated linoleic acid (CLA) affects fat deposition and lipid metabolism in mammals, including livestock. To determine CLA effects in Atlantic salmon (Salmo salar), a major farmed fish species, fish were fed for 12 weeks on diets containing fish oil or fish oil with 2% and 4% CLA supplementation. Fatty acid composition of the tissues showed deposition of CLA with accumulation being 2 to 3 fold higher in muscle than in liver. CLA had no effect on feed conversion efficiency or growth of the fish but there was a decreased lipid content and increased protein content after 4% CLA feeding. Thus, the protein:lipid ratio in whole fish was increased in fish fed 4% CLA and triacylglycerol in liver was decreased. Liver beta-oxidation was increased whilst both red muscle beta-oxidation capacity and CPT1 activity was decreased by dietary CLA. Liver highly unsaturated fatty acid (HUFA) biosynthetic capacity was increased and the relative proportion of liver HUFA was marginally increased in salmon fed CLA. CLA had no effect on fatty acid Delta6 desaturase mRNA expression, but fatty acid elongase mRNA was increased in liver and intestine. In addition, the relative compositions of unsaturated and monounsaturated fatty acids changed after CLA feeding. CLA had no effect on PPARalpha or PPARgamma expression in liver or intestine, although PPARbeta2A expression was reduced in liver at 4% CLA feeding. CLA did not affect hepatic malic enzyme activity. Thus, overall, the effect of dietary CLA was to increase beta-oxidation in liver, to reduce levels of total body lipid and liver triacylglycerol, and to affect liver fatty acid composition, with increased elongase expression and HUFA biosynthetic capacity.     

Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates

Nitric oxide (NO) is synthesized from L-arginine by NO synthase in virtually all cell types. Emerging evidence shows that NO regulates the metabolism of glucose, fatty acids and amino acids in mammals. As an oxidant, pathological levels of NO inhibit nearly all enzyme-catalyzed reactions through protein oxidation. However, as a signaling molecule, physiological levels of NO stimulate glucose uptake as well as glucose and fatty acid oxidation in skeletal muscle, heart, liver and adipose tissue; inhibit the synthesis of glucose, glycogen, and fat in target tissues (e.g., liver and adipose); and enhance lipolysis in adipocytes. Thus, an inhibition of NO synthesis causes hyperlipidemia and fat accretion in rats, whereas dietary arginine supplementation reduces fat mass in diabetic fatty rats. The putative underlying mechanisms may involve multiple cyclic guanosine-3',5'-monophosphate-dependent pathways. First, NO stimulates the phosphorylation of adenosine-3',5'-monophosphate-activated protein kinase, resulting in (1) a decreased level of malonyl-CoA via inhibition of acetyl-CoA carboxylase and activation of malonyl-CoA decarboxylase and (2) a decreased expression of genes related to lipogenesis and gluconeogenesis (glycerol-3-phosphate acyltransferase, sterol regulatory element binding protein-1c and phosphoenolpyruvate carboxykinase). Second, NO increases the phosphorylation of hormone-sensitive lipase and perilipins, leading to the translocation of the lipase to the neutral lipid droplets and, hence, the stimulation of lipolysis. Third, NO activates expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, thereby enhancing mitochondrial biogenesis and oxidative phosphorylation. Fourth, NO increases blood flow to insulin-sensitive tissues, promoting substrate uptake and product removal via the circulation. Modulation of the arginine-NO pathway through dietary supplementation with L-arginine or L-citrulline may aid in the prevention and treatment of the metabolic syndrome in obese humans and companion animals, and in reducing unfavorable fat mass in animals of agricultural importance.     

Studies on lipogenesis in vivo. Effect of dietary fat or starvation on conversion of [14C]glucose into fat and turnover of newly synthesized fat

1. Lipogenesis was studied in vivo by giving mice 250mg. meals of [U-(14)C]glucose and measuring the disposition and incorporation of label. About 48% of the (14)C dose was eliminated as (14)CO(2) in the first 2hr. At 60min. after administration, 1.0, 1.9 and 11.9% of the dose was recovered as liver glycogen, liver fatty acid and carcass fatty acid respectively. Of the [(14)C]glucose converted into fat in the epididymal pads about 90% was present as glyceride fatty acid and 10% as glyceride glycerol. 2. Hepatic synthesis of fatty acid was depressed by dietary fat to a much greater extent than was synthesis outside the liver. Both feeding with fat and starvation decreased the proportion of the label taken up by adipose tissue present as fat (triglyceride) and increased the proportion of triglyceride label present as glyceride glycerol. These results are consistent with the hypothesis that the primary action of both these conditions in decreasing fat synthesis is to inhibit synthesis of fatty acids. 3. Turnover of body fat labelled in vivo from [U-(14)C]glucose was estimated from the decline in radioactivity measured over the first 24hr. of the experiment. The half-life of liver and extrahepatic fatty acids (excluding epididymal fat) was 16hr. and 3 days respectively. In contrast, no measurable decrease in radioactivity of the fatty acids of epididymal fat was observed for 7 days after administration of the [U-(14)C]glucose.     

Effects of cholestyramine feeding on tissue lipase activities and plasma fatty acids in the pregnant rat

Rats fed a non-absorbable bile acid binding resin (cholestyramine) throughout gestation had decreased activities of adipose tissue lipoprotein lipase (LPL), hepatic triacylglycerol lipase and a heparin-releasable placental lipase distinct from LPL, when assayed at near-term gestation. The fetal plasma and liver triacylglycerol concentrations were not altered. The fetal liver total lipid and plasma triacylglycerol, however, had reduced levels of n-6 and n-3 series fatty acids, suggesting decreased availability of maternal dietary-derived essential fatty acids. These studies suggest that cholestyramine feeding may alter triacylglycerol flux and the quantity or type of maternal fatty acids available for placental transfer. The resin has application for in vivo study of the effects of maternal lipid transfer on the regulation of fetal hepatic lipid synthesis.     

Effects of somatostatin-25 on lipid mobilization from rainbow trout,Oncorhynchus mykiss,liver and adipose tissue incubated in vitro. Comparison with somatostatin-14

Summary The physiological effects of the pancreatic peptides somatostatin-14 and somatostatin-25 on lipid metabolism in rainbow trout were evaluated by in vitro culture of liver and adipose tissue. The culture medium was subsequently analyzed for glycerol and fatty acid content and triacylglycerol lipase activity was measured within the tissues. Both somatostatin-14 and somatostatin-25 stimulated hepatic fatty acid and glycerol release within 3 h after treatment. Liver triacylglycerol lipase activity was elevated following treatment with somatostatin-14 (76% above control) or somatostatin-25 (94% above control). Somatostatin-14 and somatostatin-25 also significantly stimulated the release of fatty acid and glycerol from adipose tissue. Triacylglycerol lipase activity in adipose tissue also was enhanced by both somatostatins. These results indicate that somatostatin-14 and somatostatin-25 directly stimulate the mobilization of triacylglycerol from liver and adipose tissue, suggesting that these peptides are important systemic modulators of lipid metabolism in fish.Abbreviations bw body weight - cAMP cyclic adenosine monophosphate - FA ratty acids - fw fresh weight - GLU glucagon - INS insulin - MS-222 tricaine-methane sulphonate - SS-14 somatostatin-14 - SS-25 somatostatin-25 - TG triacylglycerol     

Fatty acid synthesis in liver and adipose tissue of normal and genetically obese (ob/ob) mice during the 24-hour cycle.

1. The synthesis of long-chain fatty acids de novo was measured in the liver and in regions of adipose tissue in intact normal and genetically obses mice throughout the daily 24h cycle. 2. The total rate of synthesis, as measured by the rate of incorporation of 3H from 3H2O into fatty acid, was highest during the dark period, in liver and adipose tissue of lean or obese mice. 3. The rate of incorporation of 14C from [U-14C]glucose into fatty acid was also followed (in the same mice). The 14C/3H ratios were higher by a factor of 5-20 in parametrial and scapular fat than that in liver. This difference was less marked during the dark period (of maximum fatty acid synthesis). 4. In normal mice, the total rate of fatty acid synthesis in the liver was about twofold greater than that in all adipose tissue regions combined. 5. In obese mice, the rate of fatty acid synthesis was more rapid than in lean mice, in both liver and adipose tissue. Most of the extra lipogenesis occurred in adipose tissue. The extra hepatic fatty acids synthesized in obese mice were located in triglyceride rather than phospholipid. 6. In adipose tissue of normal mice, the rate of fatty acid synthesis was most rapid in the intra-abdominal areas and in brown fat. In obese mice, all regions exhibited rapid rates of fatty acid synthesis. 7. These results shed light on the relative significance of liver and adipose tissue (i.e. the adipose 'organ') in fatty acid synthesis in mice, on the mino importance of glucose in hepatic lipogenesis, and on the alterations in the rate of fatty acid synthesis in genetically obese mice.     

The effects of starvation and force-feeding on the metabolism of the Northern pike, Esox lucius L.

The effects of starvation and force-feeding on certain tissue and blood constituents were studied in the Northern pike, Esox lucius L. Starvation resulted in a reduction of liver and muscle glycogen and liver lipid. Blood glucose concentration and haematocrit were reduced, total plasma cholesterol levels were increased, while the levels of plasma free fatty acids (FFA), amio acid nitrogen and protein remained unaltered. No significant changes were observed in either muscle protein, muscle water or the response to amino acid loading during the starvation period.
The force-feeding of pike starved for 3 months resulted in liver lipid and muscle glycogen being increased to levels higher than those observed in freshly-captured fish. Liver glycogen, however, increased to values only slightly higher than those of starved animals. Furthermore, while force-feeding had little effect on plasma FFA or protein concentrations, blood glucose, plasma cholesterol and haematocrit returned to the levels found in freshlycaptured fish and those of amino acid nitrogen were higher.
The results indicate that pike are well adapted for periods of prolonged starvation and that hepatic and extra-hepatic lipid and glycogen stores serve for metabolic needs during food shortage, while body protein is conserved. The endocrine basis for these changes in the tissue and blood constituents is discussed.     

Changes in the biochemical composition of fat body stores during adult development of female crickets, Gryllus bimaculatus

Age-dependent changes in the fat body composition and aspects of lipogenesis in the free abdominal fat body of female crickets, Gryllus bimaculatus, were studied. Lipid, protein, glycogen, and free carbohydrate content of the fat body, and fat body wet weight increased simultaneously and sharply from day 0 onwards and were doubled/almost doubled by day 2 after adult emergence. Lipogenic activity of the fat body, fat body weight, and the energy stores in the fat body peaked on day 2, except for free carbohydrate, which peaked on day 3. On day 2, the fat body was mainly comprised of lipid (53.8%) and protein (6.6%), while glycogen and free carbohydrate together contributed less than 1% of the fat body wet weight. After peaking, both lipogenesis and energy stores decreased in a synchronous manner. The depletion of the fat body energy stores and the consequent decrease in the fat body weight were concomitant with a fast and massive gain in ovary weight (day 2: 19.5 +/- 1.5 mg; day 4: 332.8 +/- 31.5 mg) due to the vitellogenic oocyte growth that started on day 2. Our data clearly underline the importance of the free abdominal fat body as a source of energy for reproduction in the cricket. Fat body fatty acid synthase activity coincided with lipogenic activity. Adipokinetic hormone inhibits lipid synthesis in the fat body, but treatment of the fat body with adipokinetic hormone in vitro showed no consistent effect on fatty acid synthase activity.     

Lipid synthesis and deposition by adult Richardson's ground squirrels in the natural environment

Summary Adult male Richardson's ground squirrels,Spermophilus richardsonii, were estimated to have emerged from hibernation in late February to early March, and adult females in mid to late March. Half of the females trapped in late March were not pregnant, as against 10% after that time. In late March males and all females had similar WAT (white adipose tissue) deposits. Between late March and early June, WAT deposits in males increased from 14 g to 64 g (a rate of 5.6 g per week). In non-parous females WAT deposits increased from 13 g to 48 g from late March to late May (4.2 g per week). Fat deposits decreased during lactation but thereafter increased from 8 g to 29 g (a rate of 6.0 g per week) between early May and early June. In males the rate of fatty acid synthesis in BAT (brown adipose tissue), liver and WAT did not change from late March to late May, and rates in the corresponding tissues of non-pregnant females were similar to those in males. Fatty acid synthesis decreased during late pregnancy and lactation. After lactation, the rate of fatty acid synthesis in all tissues increased to that in males and non-pregnant females. Males initiated fattening 5–7 weeks earlier than females. It is concluded that compared with adult males, the later immergence of adult female Richardson's ground squirrels into hibernation is due primarily to later initiation of fattening and less to differences in rate of lipid synthesis after the reproductive period. Rates of fatty acid synthesis in liver and BAT were several times greater than that in WAT. The former tissues may contribute fatty acids for prehibernatory fattening.Abbreviations BAT brown adipose tissue - WAT white adipose tissue     

Effect of adrenaline on the activity of lipolytic enzymes in calves

The research of adrenalin influence on the lipid synthesis and split intensity and fat acid oxidation was carried out in two groups of one-month old calves of black-white breed. The animals were injected by adrenalin (1 mg/kg) during 3 days. The specimens of the musculus quadriceps extensor femoris were used for biochemical researches. The increase of the triacylglycerol lipase activity and oxidation intensity of [1-14C] palmitic and [1-14C] stearic acids and the reduction of lipoprotein lipase activity and lipid synthesis from acetic acid intensity were found during researches. So, the reciprocal dependence between lipid synthesis and fatty acid oxidation as well as the connection between processes of lipolysis and fatty acid beta-oxidation, influenced by adrenalin, were observed in the skeletal muscles of the cattle.     

Regulation of lipid flux between liver and adipose tissue during transient hepatic steatosis in carnitine-depleted rats

Rats with carnitine deficiency due to trimethylhydrazinium propionate (mildronate) administered at 80 mg/100 g body weight per day for 10 days developed liver steatosis only upon fasting. This study aimed to determine whether the transient steatosis resulted from triglyceride accumulation due to the amount of fatty acids preserved through impaired fatty acid oxidation and/or from up-regulation of lipid exchange between liver and adipose tissue. In liver, mildronate decreased the carnitine content by approximately 13-fold and, in fasted rats, lowered the palmitate oxidation rate by 50% in the perfused organ, increased 9-fold the triglyceride content, and doubled the hepatic very low density lipoprotein secretion rate. Concomitantly, triglyceridemia was 13-fold greater than in controls. Hepatic carnitine palmitoyltransferase I activity and palmitate oxidation capacities measured in vitro were increased after treatment. Gene expression of hepatic proteins involved in fatty acid oxidation, triglyceride formation, and lipid uptake were all increased and were associated with increased hepatic free fatty acid content in treated rats. In periepididymal adipose tissue, mildronate markedly increased lipoprotein lipase and hormone-sensitive lipase activities in fed and fasted rats, respectively. On refeeding, carnitine-depleted rats exhibited a rapid decrease in blood triglycerides and free fatty acids, then after approximately 2 h, a marked drop of liver triglycerides and a progressive decrease in liver free fatty acids. Data show that up-regulation of liver activities, peripheral lipolysis, and lipoprotein lipase activity were likely essential factors for excess fat deposit and release alternately occurring in liver and adipose tissue of carnitine-depleted rats during the fed/fasted transition.     

Effects of feed restriction on growth performance,lipid mobilization,and gene expression in rose spotted snapper (Lutjanus guttatus)

The effects of feed deprivation were evaluated for 1 week and 2 weeks in Lutjanus guttatus juveniles. A significant reduction in body mass was observed in both feed deprivation schemes, as well as in hepatosomatic, viscerosomatic and mesenteric fat indexes. The composition of fasted fish was characterized by a decrease in lipid content; the liver displayed an intense reduction of lipid reserves in both fasted groups, and increased expression of the lysosomal acid lipase. 1 week after re-feeding, both experimental groups showed an increase in specific growth rate, feed intake and feed conversion ratio. A recovery in hepatic lipid reserves was observed, and the expression of the lysosomal acid lipase decreased, although lipid content in both groups was still significantly lower than in control groups. Hepatic expression of the growth hormone receptor decreased after fasting, and remained low even after the fish were fed, whereas the expression of insulin-like growth factor 1 and 2 increased after fasting and decreased in both groups when fish were fed again. Altogether, these results showed a partial compensatory growth response in L. guttatus juveniles after fasting, with enhanced growth rates and improved feed efficiency. Fish used stored lipid reserves as the main energy source, and the expression of growth-related and lipid mobilization marker genes in the liver showed similar patterns in both fasting schemes. Based on the results, we suggest as much as 1-week fasting intervals during grow-out programmes to reduce visceral fat and increase growth rate in this species.

     

Hepatic overexpression of hormone-sensitive lipase and adipose triglyceride lipase promotes fatty acid oxidation, stimulates direct release of free fatty acids, and ameliorates steatosis

Hepatic steatosis is often associated with insulin resistance and obesity and can lead to steatohepatitis and cirrhosis. In this study, we have demonstrated that hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), two enzymes critical for lipolysis in adipose tissues, also contribute to lipolysis in the liver and can mobilize hepatic triglycerides in vivo and in vitro. Adenoviral overexpression of HSL and/or ATGL reduced liver triglycerides by 40-60% in both ob/ob mice and mice with high fat diet-induced obesity. However, these enzymes did not affect fasting plasma triglyceride and free fatty acid levels or triglyceride and apolipoprotein B secretion rates. Plasma 3-beta-hydroxybutyrate levels were increased 3-5 days after infection in both HSL- and ATGL-overexpressing male mice, suggesting an increase in beta-oxidation. Expression of genes involved in fatty acid transport and synthesis, lipid storage, and mitochondrial bioenergetics was unchanged. Mechanistic studies in oleate-supplemented McA-RH7777 cells with adenoviral overexpression of HSL or ATGL showed that reduced cellular triglycerides could be attributed to increases in beta-oxidation as well as direct release of free fatty acids into the medium. In summary, hepatic overexpression of HSL or ATGL can promote fatty acid oxidation, stimulate direct release of free fatty acid, and ameliorate hepatic steatosis. This study suggests a direct functional role for both HSL and ATGL in hepatic lipid homeostasis and identifies these enzymes as potential therapeutic targets for ameliorating hepatic steatosis associated with insulin resistance and obesity.     

Effects of long-term starvation on body weight and body composition of juvenile channel catfish, Ictalurus punctatus, with special emphasis on amino acid and fatty acid changes

Triplicate groups of 30 channel catfish Ictalurus punctatus (initial weight: 76.13 ± 0.78 g) were stocked in indoor flow‐through fiberglass tanks and starved for 80 days. Body weight, morphometric parameters, body composition, amino acid and fatty acid changes in muscle and liver tissues were investigated to determine the effect of long‐term starvation on body weight and body composition of juvenile channel catfish. During the starvation period, body weight, condition factor (CF), viscerosomatic index (VSI), hepatosomatic index (HSI) and intraperitoneal fat ratio (IPR) declined (P < 0.05). In the whole body, both protein and lipid decreased while changes in the amount of fat were relatively rapid. Hepatic lipid and carbohydrate contents declined as starvation progressed, but crude protein and moisture contents increased (P < 0.05). In contrast, muscle crude protein showed a greater decline than did muscle lipids, and muscle glycogen remained relatively constant. During the 80‐day starvation period the ratio of total essential amino acids (EAA) to total non‐essential amino acids (NEAA) in muscle and liver (P < 0.05) increased. In muscle tissue, total mono‐unsaturated fatty acids (MUFA) and n‐6 fatty acids decreased, but total saturated fatty acids (SFA) and n‐3 fatty acids, as well as the ratio of n‐3 to n‐6 fatty acids increased (P < 0.05). However, in the liver, starvation resulted in the relative increase of total MUFA and reduction in n‐3 fatty acid contents as well as the ratio of n‐3 to n‐6 fatty acids (P < 0.05). Based on these observations, lipids and glycogen can be considered as more important sources of catabolizable energy in liver, whereas protein might be preferentially mobilized in muscle; lipids played a more important role as energy reserves on a relative basis in the whole body. Channel catfish preferentially utilized NEAA to EAA as an energy substrate and preferentially reserved EAA during starvation. Mobilization of fatty acids showed more variation in the muscle and liver during starvation.     

The influence of diet on the lipogenic response to thyroxine in rat liver.

ATP citrate lyase, acetyl-CoA synthetase, malic enzyme and hexose monophosphate dehydrogenase activities and rates of $\text{denovo}$ synthesis of long chain fatty acids from labeled acetate and citrate were measured in cell-free fractions of liver from rats fed various diets, with and without D- or L- thyroxine. Diets containign sucrose (vs. isocaloric glucose) or lard (vs. isocaloric corn oil) stimulated hepatic lipogenesis both in control and in thyroxine-treated rats. The lipogenic response to thyroxine was greatly modified by diet, except for an invariable rise in malic enzyme activity. With diets providing less than 6% of calories as linoleic acid, thyroxine increased fatty acid synthesis, depleted liver glycogen and retarded growth; when linoleic acid was increased to 16% of calories, thyroxine had no effect on fatty acid synthesis or growth and liver glycogen depletion was significantly attenuated. This response to dietary linoleic acid suggests that these phenomena may be largely secondary to the increased requirement for essential fatty acid in thyrotoxicosis. Further study should reveal the extent to which observed effects of excess thyroid hormone are amenable to control by dietary polyunsaturated fat.