Acid Synthesis In Adipose Tissue Research Articles

Enzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues.

SummaryFatty acid synthase (FASN) predominantly generates straight-chain fatty acids using acetyl-CoA as the initiating substrate. However, monomethyl branched-chain fatty acids (mmBCFAs) are also present in mammals but thought to be primarily diet-derived. Here we demonstrate that mmBCFAs are de novo synthesized via mitochondrial BCAA catabolism, exported to the cytosol by adipose-specific expression of carnitine acetyltransferase (CrAT), and elongated by FASN. Brown fat exhibits the highest BCAA catabolic and mmBCFA synthesis fluxes, whereas these lipids are largely absent from liver and brain. mmBCFA synthesis is also sustained in the absence of microbiota. We identify hypoxia as a potent suppressor of BCAA catabolism that decreases mmBCFA synthesis in obese adipose tissue, such that mmBCFAs are significantly decreased in obese animals. These results identify adipose tissue mmBCFA synthesis as a novel link between BCAA metabolism and lipogenesis, highlighting roles for CrAT and FASN promiscuity that influence acyl-chain diversity in the lipidome.

Effects of delta-tocotrienol on obesity-related adipocyte hypertrophy, inflammation and hepatic steatosis in high-fat-fed mice

Inflammation is a major underlying cause for obesity-associated metabolic diseases. Hence, anti-inflammatory dietary components may improve obesity-related disorders. We hypothesized that delta-tocotrienol (δT3), a member of the vitamin E family, reduces adiposity, insulin resistance and hepatic triglycerides through its anti-inflammatory properties. To test this hypothesis, C57BL/6J male mice were fed a high-fat diet (HF) with or without supplementation of δT3 (HF+δT3) at 400 mg/kg and 1600 mg/kg for 14 weeks, and they were compared to mice fed a low-fat diet (LF) or HF supplemented with metformin as an antidiabetic control. Glucose tolerance tests were administered 2 weeks prior to the end of treatments. Histology, quantitative polymerase chain reaction and protein analyses were performed to assess inflammation and fatty acid metabolism in adipose and liver tissues. Significant improvements in glucose tolerance, and reduced hepatic steatosis and serum triglycerides were observed in δT3-supplemented groups compared to the HF group. Body and fat pad weights were not significantly reduced in HF+δT3 groups; however, we observed smaller fat cell size and reduced macrophage infiltration in their adipose tissues compared to other groups. These changes were at least in part mechanistically explained by a reduction of mRNA and protein expression of proinflammatory adipokines and increased expression of anti-inflammatory adipokines in HF+δT3 mice. Moreover, δT3 dose-dependently increased markers of fatty acid oxidation and reduced markers of fatty acid synthesis in adipose tissue and liver. In conclusion, our studies suggest that δT3 may promote metabolically healthy obesity by reducing fat cell hypertrophy and decreasing inflammation in both liver and adipose tissue.

Ablation of gp78 in Liver Improves Hyperlipidemia and Insulin Resistance by Inhibiting SREBP to Decrease Lipid Biosynthesis

gp78 is a membrane-anchored ubiquitin ligase mediating the degradation of HMG-CoA reductase (HMGCR) and Insig-1. As a rate-limiting enzyme in cholesterol biosynthesis, HMGCR undergoes rapid sterol-promoted degradation. In contrast, destruction of Insig-1 releases its inhibition on SREBP and stimulates the expression of lipogenic genes. Thus, gp78 has opposite effects on lipid biosynthesis. We here generated liver-specific gp78 knockout (L-gp78(-/-)) mice and showed that although the degradation of HMGCR was blunted, SREBP was suppressed due to the elevation of Insig-1/-2, and therefore the lipid biosynthesis was decreased. The L-gp78(-/-) mice were protected from diet-/age-induced obesity and glucose intolerance. The livers of L-gp78(-/-) mice produced more FGF21, which activated thermogenesis in brown adipocytes and enhanced energy expenditure. Together, the major function of gp78 in liver is regulating lipid biosynthesis through SREBP pathway. Ablation of gp78 decreases the lipid levels and increases FGF21, and is beneficial to patients with metabolic diseases.

Critical Role of Peroxisome Proliferator Activated Receptor-δ on Body Fat Reduction in C57BL/6J and Human Apolipoprotein E2 Transgenic Mice Fed Delipidated Soybean

The consumption of soy protein and fiber reduces body fat accumulation; however, the mechanism of this effect has not been clearly understood. We investigated the antiobesogenic effect of soy protein and fiber in two different mouse models. Normolipidemic nonobese C57BL/6J and hyperlipidemic obese human apolipoprotein E2 transgenic mice were fed either delipidated soybean (DLSB) containing soy protein and fiber or a control diet. The DLSB-fed mice showed a significant reduction in body weight gain and adiposity compared with controls, in both C57BL/6J and apoE2 mice. All metabolic parameters were significantly improved in the DLSB group compared with controls: total cholesterol, low-density lipoprotein cholesterol, insulin, and leptin levels were significantly reduced. Adiponectin concentrations were significantly elevated, and glucose tolerance was improved. In both types of DLSB-fed mice, the specific induction of PPAR-δ protein expression was evident in muscle and adipose tissues. The expression of PPAR-δ target genes in the DLSB-fed mice was also significantly altered. Acetyl-CoA carboxylase-1 and fatty acid synthase levels in adipose tissue were downregulated, and uncoupling protein-2 in muscle was upregulated. Intestinal expression of fatty acid transport protein-4, cluster of differentiation-36, and acyl-CoA synthetase were significantly downregulated. We propose that marked activation of PPAR-δ is the primary mechanism mediating the antiobesogenic effect of soybean and that PPAR-δ has multiple actions: induction of thermogenesis in muscle, reduction of fatty acid synthesis in adipose tissue, and reduction of fatty acid uptake in intestinal tissue.

Dietary Supplementation with α-Amylase Inhibitor Wheat Albumin to High-Fat Diet-Induced Insulin-Resistant Rats Is Associated with Increased Expression of Genes Related to Fatty Acid Synthesis in Adipose Tissue

It is well-known that insulin resistance induces lipid abnormalities by decreasing insulin actions in adipose tissue. This study examined the effects of inhibiting postprandial hyperglycemia/hyperinsulinemia, using the alpha-amylase inhibitor wheat albumin (WA), on the expression of genes related to fatty acid metabolism in the adipose tissue of high-fat diet-induced insulin-resistant rats. Postprandial glucose and insulin levels were significantly lower after oral starch loading with WA than with inactivated WA in insulin-resistant rats. In addition, the increases in the plasma triacylglycerol and insulin levels by feeding insulin-resistant rats a control diet were inhibited by WA supplementation. Supplementation with WA increased the mRNA levels of not only fatty acid synthase (FAS) and acyl-CoA carboxylase (ACC) but also their transcriptional factors such as carbohydrate response element-binding protein (ChREBP) and sterol regulatory element binding protein (SREBP)1 in the mesenteric adipose tissue of the insulin-resistant rats. In addition, supplementation with WA tended to increase the protein expression levels of FAS and ACCs. These results suggest that reductions in the plasma triacylglycerol and insulin levels by inhibiting hyperglycemia/hyperinsulinemia with the alpha-amylase inhibitor WA in high-fat diet-induced insulin-resistant rats are associated with increased expression of genes related to fatty acid synthesis and their transcriptional factors in adipose tissue.

Identification of Dicarboxylate Carrier Slc25a10 as Malate Transporter in de Novo Fatty Acid Synthesis

Mitochondrial solute carrier family 25 member 10 (Slc25a10) transports dicarboxylates such as malate or succinate across the mitochondrial inner membrane. Although fatty acid synthesis in adipose tissue or the liver is initiated by citrate transport in exchange for malate across the mitochondrial membrane, the transporter responsible for supplying malate during citrate transport has not been identified. In the present study, we clarified the role of Slc25a10 in supplying malate for citrate transport and examined the effect of Slc25a10 suppression on the lipogenic pathway and lipid accumulation. We have reported an Slc25a10 increase in white adipose tissue in obese mouse models and a decrease in a fasted mouse model using expression profiles. Next, we examined the effect of Slc25a10 suppression by small interfering RNA on citrate transport in the lipogenic cell lines HepG2 and 3T3-L1. We observed that inhibition of malate transport by Slc25a10 suppression significantly reduced the citrate transport from the mitochondria to the cytosol. We also found that suppression of Slc25a10 down-regulated the lipogenic pathway, indicated by decreases in ACC1 expression and malonyl-CoA level. Furthermore, suppression of Slc25a10 decreased triglyceride lipid accumulation in adipose-differentiated 3T3-L1 cells. These results suggested that Slc25a10 plays an important role in supplying malate for citrate transport required for fatty acid synthesis and indicated that inhibition of Slc25a10 might effectively reduce lipid accumulation in adipose tissues.

Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver

The escort protein SCAP transports SREBPs from ER to Golgi where the active domains are released to activate genes for fatty acid (FA) and cholesterol synthesis. Mice with conditional SCAP deficiency in liver (L-Scap-) manifest marked reductions in hepatic lipid synthesis. Here, we show that the decreased FA synthesis in liver is balanced by an equal increase in nonhepatic tissues, primarily adipose tissue. Extrahepatic synthesis of FAs preserves adipose mass, even when L-Scap- mice consume a fat-free diet. This compensatory response disappears upon fasting, implicating a role for insulin, the major hormonal activator of FA synthesis. This response is mediated by an insulin-dependent increase in adipocyte SREBP-1c and its target mRNAs. In epididymal fat of L-Scap- mice, phosphorylated Akt, Glut-4 mRNA, and glucose uptake are also increased, indicating insulin hypersensitivity. Plasma VLDL triglycerides are dramatically reduced in L-Scap- mice, underscoring the benefits of synthesizing FAs in fat rather than liver.

Captopril enhanced insulin-stimulated glycogen synthesis in skeletal muscle but not fatty acid synthesis in adipose tissue of hereditary hypertriglyceridemic rats

In addition to their hypotensive action, angiotensin-converting enzyme (ACE) inhibitors exert a beneficial effect on glucoregulation. In the present study, the effect of ACE inhibition by captopril on glucose utilization in peripheral tissues was investigated in non-obese rats with hereditary hypertriglyceridemia (HHTg) associated with hyperinsulinemia and insulin resistance. Normotriglyceridemic Wistar rats served as controls (C). Rats of both groups received a high-sucrose diet, and a half of each group also captopril in drinking water (10 mg/kg body weight [bw]) for 2 weeks. Captopril administration reduced fasting glycemia and postprandial triglyceridemia in HHTg rats, while the fasting levels of nonesterified fatty acids (NEFA), glycerol, and lactate were decreased in both groups. The sensitivity of skeletal muscle to insulin action evaluated as in vitro 14C-glucose incorporation into glycogen was significantly increased by captopril treatment both in HHTg (3.51 ± 0.48 v 2.0 ± 0.12 μmol glucose/g wet weight [ww]) and C (3.32 ± 0.21 v 2.48 ± 0.09 μmol glucose/g ww). In isolated adipose tissue, the insulin-stimulated 14C-glucose incorporation into neutral lipids was increased, after captopril administration, by 137% in C and by 35% only in HHTg. After captopril treatment, insulin-stimulated de novo fatty acid synthesis rose significantly in C while remaining low in HHTg. The increase in esterification was comparable in both groups. Separate experiments were designed to assess the possible involvement of bradykinin in mediating captopril action. Both C and HHTg rats fed a high-sucrose diet for 2 weeks were treated with captopril (50 mg/kg orally) for 1 hour; half of each group received the specific inhibitor of bradykinin receptor HOE-140 (100 μg/kg intraperitoneally [IP]) 1 hour before captopril administration. In C, captopril administration enhanced the insulin-stimulated in vitro glucose incorporation into lipids in adipose tissue by 255%, and into glycogen in the musculus soleus by 45%; this effect was eliminated by HOE-140. In HHTg, neither a single dose of captopril nor HOE-140 had any effect. We conclude that long-term captopril administration increased the insulin sensitivity of peripheral tissue in both C and HHTg rats, but with different efficacy. While the insulin-sensitizing action of captopril on skeletal muscle was comparable in HHTg and C rats, there were differences in the effect of captopril on adipose tissue. The difference became particularly manifest in de novo fatty acid synthesis.

Acetyl-CoA carboxylase- : Gene structure-function relationships

Acetyl-CoA carboxylase-α (ACC-α) is a key enzyme in the regulation of fatty acid synthesis and is subject to both acute control, via reversible phosphorylation, and chronic control that results in the regulation of synthesis of the enzyme. The gene for ACC-α is expressed ubiquitously, but expression is highest in lipogenic tissues: adipose, liver, and lactating mammary gland. These tissues demonstrate a metabolic adaptation to changing physiological demands; for example, during lactation fatty acid synthesis in adipose tissue is markedly repressed, resulting in the partitioning of lipogenic precursors to the mammary gland. Lipogenic tissues can also exhibit dysfunctions that result in excess fat deposition in farm animals and obesity in humans. Transcription of the ACC-α gene is initiated from multiple promoters in a tissue-specific fashion. Promoter II (PII) transcripts are present in all tissues, whereas promoter I (PI) transcripts are principally restricted to adipose tissue. We have also identified an additional promoter (PIII) that is also expressed in a tissue-restricted manner. All three promoters are modulated by the physiological state of an animal, suggesting that each promoter possesses enhancer domains that are targets for cell-specific signaling pathways and act in concert with the basal transcriptional machinery to regulate expression of the gene. For example, expression of the ACC-α gene is increased in mammary gland during lactation concomitant with the increase in the rate of fatty acid synthesis; in sheep this arises through induction of both PII and PIII promoter activities. Conversely, the ACC-α gene is repressed in sheep adipose tissue during lactation, and this occurs primarily through inactivation of PI, although PII activity is also repressed. This may arise in part from a change in sensitivity of the tissue to insulin. Analysis of the structure and function of the various promoters of ACC-α is presented with a view to determining the molecular basis of the modulation of expression of this gene in lipogenic tissues.

Endocrine control of sheep adipose tissue fatty acid synthesis: depot specific differences in response to lactation.

The effects of lactation and insulin, growth hormone and dexamethasone (a glucocorticoid analogue) have been assessed on the rate of fatty acid synthesis in adipose tissue from omental (abdominal), subcutaneous and popliteal (intermuscular) depots of sheep. Adipocyte mean cell volume was greatest in omental tissue but the rate of fatty acid synthesis was similar in omental and subcutaneous adipose tissue in non-lactating ewes. Insulin increased the rate of fatty acid synthesis in tissue from all three depots and this was antagonised by growth hormone. The effects of growth hormone were less in omental adipose tissue from non-lactating sheep than in the other two depots. Lactation decreased the rate of fatty acid synthesis in all three depots, but to a lesser extent in omental than the other depots. Insulin resistance was apparent in subcutaneous and popliteal tissues from lactating ewes but not in omental tissue. Omental adipose tissue, thus differs in several aspects from the two carcass depots. Differences in response to hormones in omental adipose tissue were apparent in young sheep before the onset of fattening when omental adipocytes are similar in size to subcutaneous adipocytes.

Effect of the entero-pancreatic hormones, gastric inhibitory polypeptide and glucagon-like polypeptide-1(7–36) amide, on fatty acid synthesis in explants of rat adipose tissue

The effect of gastric inhibitory polypeptide (GIP), glucagon-like peptide-1(7-36) amide, (GLP-1(7-36) amide), glucagon-like peptide-2 (GLP-2), glucagon and insulin on fatty acid synthesis in explants of rat adipose tissue from various sites was investigated. GIP, GLP-1(7-36) amide and insulin stimulated fatty acid synthesis, as determined by measuring the incorporation of [14C]acetate into saponifiable fat, in a dose-dependent manner, over the concentration range 5-15 ng/ml (0.87-2.61 nmol/l) for insulin and 0.5-7.5 ng/ml for GIP (0.10-1.50 nmol/l) and GLP-1(7-36) amide (0.15-2.27 nmol/l). Insulin and GIP caused a significantly greater stimulation of [14C]acetate incorporation into fatty acids in omental adipose tissue than in either epididymal or subcutaneous adipose tissue. Both GIP and GLP-1(7-36) amide had the ability to stimulate fatty acid synthesis within the physiological range of the circulating hormones. At lower concentrations of the hormones, GLP-1(7-36) amide was a more potent stimulator of fatty acid synthesis than GIP in omental adipose tissue culture; the basal rate of fatty acid synthesis was 0.41 +/- 0.03 pmol acetate incorporated/mg wet weight tissue per 2 h; at 0.10 nmol hormone/1 1.15 +/- 0.10 and 3.40 +/- 0.12 pmol acetate incorporated/mg wet weight tissue per 2 h for GIP and GLP-1(7-36) amide respectively (P less than 0.01). GLP-2 and glucagon were without effect on fatty acid synthesis in omental adipose tissue. The study indicates that GIP and GLP-1(7-36)amide, in addition to stimulating insulin secretion, may play a direct physiological role in vivo, in common with insulin, in promoting fatty acid synthesis in adipose tissue.

Depot specific endocrine control of fatty acid synthesis in adipose tissues of foetal lambs

Chronic endocrine control of fatty acid synthesis in perirenal and subcutaneous adipose tissues of foetal lambs has been investigated. Maintenance of explants of subcutaneous adipose tissue in culture for 48 hr with insulin and dexamethasone (a glucocorticoid analogue), either singly or in combination showed that the two acted synergistically to increase the rate of fatty acid synthesis. Growth hormone inhibited the ability of insulin plus dexamethasone to increase the rate of fatty acid synthesis in explants of subcutaneous adipose tissue. In contrast neither insulin nor dexamethasone either singly or together increased the rate of fatty acid synthesis in perirenal adipose tissue; growth hormone also had no effect on the rate of fatty acid synthesis in this depot. These studies show that fatty acid synthesis is under distinct endocrine control in subcutaneous and perirenal adipose tissues in foetal lambs.

Roles of insulin and growth hormone in the adaptations of fatty acid synthesis in white adipose tissue during the lactation cycle in sheep

1. Lactation results in a substantial fall in the rate of fatty acid synthesis in sheep adipose tissue. 2. Maintenance of adipose tissue from non-lactating sheep in tissue culture for 24 or 48 h with insulin increased the rate of fatty acid synthesis. Dexamethasone, a glucocorticoid analogue, alone inhibited the rate of fatty acid synthesis, but enhanced the stimulatory effect of insulin. Growth hormone (somatotropin) antagonized the increase in the rate of fatty acid synthesis induced by insulin or insulin plus dexamethasone. 3. Maintenance of adipose tissue from lactating sheep in tissue culture resulted in a small increase in the rate of fatty acid synthesis after 24 h, and then a large increase in rate between 24 and 48 h of culture. The increase during the second 24 h period was dependent on the presence of insulin; this effect was enhanced by dexamethasone and inhibited by growth hormone. 4. The increase in the rate of fatty acid synthesis in tissue from non-lactating sheep and in tissue from lactating sheep during the major increase in rate was prevented by actinomycin D, an inhibitor of transcription. 5. Effects of insulin and growth hormone were observed with physiological concentrations of the hormones. 6. The study suggests that known changes in the serum concentrations of insulin and growth hormone are the primary causes of the changes in fatty acid synthesis in adipose tissue during the lactation cycle in sheep. 7. During lactation, adipose tissue becomes refractory to insulin in sheep; responsiveness is partly restored by tissue culture in the presence of insulin and dexamethasone.

Enzymes of glucose and fatty acid metabolism of liver, kidney, skeletal muscle, adipose tissue and mammary gland of lactating and non-lactating sheep.

The effect of peak lactation on the activities of a number of enzymes of glucose and lipid metabolism of perirenal and subcutaneous adipose tissue, skeletal muscle, liver, kidney cortex and mammary parenchyma of sheep are described. Enzymes studied included hexokinase (glucose utilization), pyruvate carboxylase (gluconeogenesis), pyruvate dehydrogenase (glucose oxidation and production of acetyl CoA for fatty acid synthesis), acetyl CoA carboxylase (fatty acid synthesis) and glycerol-3-phosphate acyltransferase (fatty acid esterification). Major changes that were found include a decrease in activities of enzymes of fatty acid synthesis and esterification in adipose tissues, decreased activity of pyruvate dehydrogenase in muscle and adipose tissues and increased pyruvate carboxylase; there was no change in activities of enzyme of fatty acid esterification in liver. Activities of hexokinase, acetyl CoA carboxylase and glycerol-3-phosphate acyltransferase have been estimated per tissue; this shows the quantitative importance of limiting glucose utilization by muscle and of suppression of fatty acid synthesis in adipose tissue for efficient partitioning of nutrients for milk production.

Effect of Continuous and Discontinuous Intravenous or Intragastric Total Parenteral Nutrition in Rats on Serum Lipids, Liver Lipids and Liver Lipogenic Rates

Lipogenesis and evidence of fat accumulation in the liver were investigated in adult male rats fed a hypertonic dextrose diet by continuous (C) and discontinuous (D) intravenous (IV) or intragastric (IG) infusion for 14 d. Rats fed by the IV and IG route were infused continuously and discontinuously (2100-0900) with 55 ml/d of a solution containing 30% dextrose and 2.72% amino acids plus vitamins and minerals. An orally (Or) fed group was fed 21.2 g of a solid diet, which provided an equivalent amount of calories and nitrogen as the infusion diet. Serum lipids, glucose, and insulin levels, de novo fatty acid synthesis in adipose tissue and liver, and the content of liver lipids were not altered by feeding the diet IV or IG. De novo lipogenesis was elevated in the livers of the continuously and discontinuously infused IV- or IG-fed rats compared with Or-fed rats. Fat accumulated in the livers of the rats infused continuously but not in the livers of the rats fed DIV, DIG or Or. Discontinuous feeding was associated with the mobilization of fatty acids that are necessary for lipoprotein formation and transport from the liver, which may explain, in part, why discontinuously infused rats do not develop fatty livers. These data indicate that cycling the total parenteral infusion may have clinical importance.

Fatty acid synthesis from amino acids in sheep adipose tissue

1. 1. The rates of incorporation of 14C from 14C labelled acetate, glucose, alanine, leucine, isoleucine and valine into fatty acids has been measured in perirenal adipose tissue from foetal lambs and 8-month-old sheep, and into both fatty acids and acylglycerol glycerol in adipose tissue from 3-year-old sheep and 220–240 g female rats. 2. 2. Rates of incorporation of 14C from amino acids into fatty acids were much lower in adipose tissue from sheep (at all three ages) than from rats, whereas rates of incorporation of 14C into acylglycerol glycerol were either greater in sheep adipose tissue or the same as in rat adipose tissue. 3. 3. The rate of incorporation of 14C from amino acids into fatty acids decreased in the order leucine > alanine > isolcucine > valine in adipose tissue from rats and foetal lambs, and in the order leucine > alanine = isoleucine > valine in adipose tissue from 8-month- and 3-year-old sheep. 4. 4. Amino acids make a very small contribution to fatty acid synthesis in adipose tissue from sheep at all stages of development examined while fatty acids are a minor product of amino acid metabolism in sheep adipose tissue. 5. 5. The study provides further evidence for an important role for ATP-citrate lyase in restricting the utilization of acetyl-CoA generated in the mitochondria for fatty acid synthesis.

Adaptations of adipose tissue metabolism and number of insulin receptors in pregnant sheep

1. 1. The endocrine control of adipose tissue metabolism during pregnancy in sheep has been investigated. 2. 2. The number of insulin receptors of sheep adipocytes was increased during pregnancy. 3. 3. There was no apparent change in the concentration of serum insulin during pregnancy in sheep while the rise in serum progesterone concentration was smaller and more gradual than in rats. 4. 4. Net lipid deposition in adipocytes occurred during the first 55 days of pregnancy, probably due primarily to increased lipoprotein lipase activity. 5. 5. Net deposition of lipid had ceased by mid-pregnancy while by 125 days of pregnancy, the rate of fatty acid synthesis in adipose tissue was decreased and the serum fatty acid concentration had risen, suggesting the onset of net lipid mobilization in the tissue. 6. 6. Results are compared with those from other studies with rats; it would appear that different mechanisms regulate lipid deposition during pregnancy in sheep and rats.

Fatty acid synthesis in adipose tissues of physically trained rats in vivo.

The effect of physical training on fatty acid synthesis in vivo was studied. After the rats had free access to a running wheel for 50 days, the rate of fatty acid synthesis estimated using 3H2O in adipose tissues of trained rats was about three times higher than that of sedentary rats in both the light and dark period. The rate of fatty acid synthesis in the liver but not in the brown adipose tissue was also slightly enhanced by physical training. The number of adipocytes was not affected, but the size of adipocytes was reduced by physical training. In trained rats, the rate of fatty acid synthesis in adipocytes whose diameter was similar to that of sedentary rats was about 10 times higher than that of sedentary rats. Within adipose tissue, the rate of fatty acid synthesis correlated positively to the diameter of adipocytes both in the sedentary and trained rats. These findings mean that the adaptive increase in fatty acid synthesis seen in adipocytes of trained rats is not secondary to the reduction in size of adipocytes.

Lipogenesis in the sand rat (Psammomys obesus).

Synthesis of fatty acids was measured in the liver and in epididymal adipose tissue of sand rats and albino rats. In chow-fed sand rats the rate of hepatic lipogenesis, as measured by the incorporation of 3H2O into fatty acids, was four- to sevenfold higher than in albino rats and in sand rats on a low-calorie saltbush diet. The contribution of [14C]glucose to lipogenesis in sand rat liver was lower than in albino rats. In fed sand rats lipogenesis incorporating 3H2O was stimulated by casein but not by glucose. In adipose tissue, lipogenesis measured 1 h after administration of 3H2O was much lower in sand rats than in albino rats. In vitro incorporation of [14C]glucose or acetate into adipose tissue fatty acids was negligible. In adipose tissue, uptake of very-low-density lipoproteins (VLDL) and lipoprotein lipase activity were sevenfold higher than in albino rats. Activities of NADP-malate dehydrogenase, acetyl CoA carboxylase, and fatty acid synthetase were considerably higher in the liver of chow-fed sand rats than in albino rats. It was concluded that obesity in sand rats originates from hepatic lipogenesis without a significant contribution of local fatty acid synthesis in adipose tissue.

Fatty acid and acylglycerol glycerol synthesis in isolated liver cells from foetal lambs

1. 1. The rates of fatty acid and acylglycerol glycerol synthesis from acetate, glucose and l-lactate in isolated liver cells from foetal lambs at about 30 and 3 days before birth are reported. The total rates of fatty acid synthesis from endogenous precursors and added substrates, measured using 3H 2O, are also reported for these liver cells. 2. 2. The total rate of fatty acid synthesis did not differ at the two ages. Of the added substrates, acetate and l-lactate were better precursors for fatty acid synthesis than glucose under the conditions used. Endogenous precursors, probably glycogen glucose, made a substantial contribution to fatty acid synthesis. 3. 3. Results are compared with previous studies of fatty acid synthesis in adipose tissue from foetal lambs.