The effects of meal feeding on the incorporation of D-[U-14C]-glucose into tissue lipids and glycogen as a function of increasing intravenous glucose dose.

The in vivo incorporation of D-[U-¹⁴C]-glucose into lipids and glycogen of adipose tissues, muscle tissues, and liver was measured 1 hr after the i.v. injection of increasing glucose doses (0.75, 1.5 and 2.5 g glucose/kg of body weight) in meal-fed and ad libitum-fed rats. In both perirenal and epididymal fat tissue, the levels of ¹⁴C-label in the total lipid extract was significantly higher in meal-fed than in nibbling rats at all glucose doses. As the glucose dose increased, the ¹⁴C-label in the lipids of both adipose tissues in meal-fed rats increased more than would be expected, assuming a linear dose dependency. In adipose tissues of nibbling rats, glucose dose dependency was linear. The ¹⁴C radioactivity in heart muscle lipids was significantly higher in meal-fed rats at all three glucose doses. In the diaphragm, this effect was seen only at the two higher doses; in liver, only at the highest dose; in skeletal muscle, there was no difference at any of the dose levels. The incorporation of ¹⁴C-label into tissue glycogen exhibited an entirely different pattern. Muscle glycogen synthesis tended to reach a plateau at the middle glucose dose in meal-fed rats, whereas it increased sharply with increasing glucose dose in nibbling rats. Indeed, muscle glycogen synthesis was much greater in nibbling rats than would be expected, assuming linear dose dependency. It was concluded that the two groups of rats responded quite differently to the increasing glucose load. The excess glucose tended to be incorporated into lipid in meal-fed rats and to muscle glycogen in nibbling rats.     

Metabolism of intravenously injected 14 C-glucose in weanling rats with hypothalamic obesity

Weanling male rats with bilateral lesions in the ventromedial hypothalamic nuclei (VMN) and sham-operated controls were injected intravenously with ¹⁴C-glucose to compare plasma glucose disappearance rates, and lipid and glycogen synthesis in liver, diaphragm, and epididymal adipose tissue. Removal of ¹⁴C-glucose from plasma was more than twice as rapid in VMN rats as in control animals despite comparable glucose levels. Incorporation of ¹⁴C-glucose into lipid was increased in all three tissues of VMN rats and was primarily due to an increase in fatty acid synthesis. Incorporation of label into glycogen by VMN rats was increased in adipose tissue but unchanged in liver and diaphragm. The results indicate that weanling VMN rats exhibit increase glucose utilization in vivo primarily directed toward lipogenesis. This finding is not restricted to adipose tissue but is present as well in liver and muscle.     

The effect of oxytetracycline on the response to insulin of diaphragm muscle and on lipid synthesisin vivo andin vitro in the ob/ob mouse

Summary The insulin sensitivity of the peripheral tissues in ob/ob mice treated with oxytetracydine was assessed bothin vivo andin vitro by measuring the effect of insulin on the incorporation of glucose into glycogen in diaphragm muscle and on the incorporation of glucose and³H₂O into lipids in epididymal adipose tissue. The results indicated that OTC treatment improved the insulin sensitivity of muscle but not that of adipose tissue. The results presented also indicated that oxytetracycline treatment led to a decrease in the basal incorporation of lipids into the liverin vivo and the adipose tissuein vivo andin vitro. The results are discussed in view of the relative importance of liver and adipose tissue in the lipid metabolism of ob/ob and lean mice and in view of results obtained by other workers on the effects of B -cell cytotoxic agents.     

Benign pancreatic hyperenzymemia: A pediatric experience

Cholesterol metabolism was studied in jejunal mucosa of the rat with special emphasis on cholesterol synthesis of villous cells, the site of intestinal lipid absorption. The type of diet and nutritional state clearly affected the cholesterologenesis of villous cells. Consequently, the incorporation of ¹⁴C-acetate into nonsaponifiable lipids (NSL; includes squalene and sterols) decreased in the following order of magnitude: 1) fat-free diet supplemented with safflower oil (FFD-SO), 2) FFD alone, 3) standard rat chow, 4) 1% cholesterol in FFD-SO, 5) total fast. Both the cholesterol feeding and the fast increased the total cholesterol concentrations in the villous cells, but the concentrations were unaffected by the other diets. In rats fed FFD-SO diet the cholesterol synthesis was significantly higher in the villous than in the crypt cells, although the cellular cholesterol concentrations were similar. The hepatic cholesterol synthesis from ¹⁴C-acetate was low in rats fed FFD-SO as compared with chow diet, whereas the incorporation of ¹⁴C-acetate into hepatic fatty acids and the incorporation of ³H-mevalonate into NSL were not affected by the diet. 5% cholestyramine had no significant effect on the cholesterol synthesis or cholesterol concentrations of the villous cells during high (FFD-SO diet) or low cholesterol synthesis (chow or cholesterol feeding). FFD-SO increased serum total cholesterol compared with chow diet and total fast, whereas cholestyramine and cholesterol feeding had no effect. Intraperitoneal administration of the hypocholesterolemic agent, 4-aminopyrazolo-pyrimidine, to fasting rats decreased markedly crypt cell cholesterol and increased cholesterol synthesis in the crypt cells and in the villous cells. The results suggest that the cholesterol synthesis of jejunal mucosa is regulated mainly by the intestinal fat absorption, dietary and serum cholesterol, and the nutritional state.     

Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells

Aims/hypothesis The aim of this study was to determine whether adiponectin elicits glucose uptake via increased GLUT4 translocation and to investigate the metabolic fate of glucose in skeletal muscle cells treated with globular adiponectin.Materials and methods Basal and insulin-stimulated 2-deoxy-d-[³H]glucose uptake, cell surface myc-tagged GLUT4 content, production of ¹⁴CO₂ by oxidation of d-[U-¹⁴C]glucose and [1-¹⁴C]oleate, and incorporation of d-[U-¹⁴C]glucose into glycogen and lactate were measured in the presence and absence of globular adiponectin.Results RT-PCR and Western blot analysis revealed that L6 cells and rat skeletal muscle cells express AdipoR1 mRNA and protein. Globular adiponectin increased both GLUT4 translocation and glucose uptake by increasing the transport V_max of glucose without altering the K_m. Interestingly, the incorporation of d-[U-¹⁴C]glucose into glycogen under basal and insulin-stimulated conditions was significantly decreased by globular adiponectin, whereas lactate production was increased. Furthermore, globular adiponectin did not affect glucose oxidation, but enhanced phosphorylation of AMP kinase and acetyl-CoA carboxylase, and fatty acid oxidation.Conclusions/interpretation The present study is the first to show that globular adiponectin increases glucose uptake in skeletal muscle cells via GLUT4 translocation and subsequently reduces the rate of glycogen synthesis and shifts glucose metabolism toward lactate production. These effects are consistent with the increased phosphorylation of AMP kinase and acetyl-CoA carboxylase and oxidation of fatty acids induced by globular adiponectin.     

Blunted muscle responsiveness to insulin in the neonatal rat

Peripheral muscle responsiveness to insulin was studied in neonatal rats in vivo by measuring net incorporation of radiolabeled glucose to glycogen in diaphragm. D(U-¹⁴C) glucose, 0.03 μCi/g rat pup weight, was injected i.p. with or without (control) insulin 5000 μU/g rat pup weight into pups from 86 litters of Sprague-Dawley rats as well as into 16 adult rats by the technique of Rafaelson. Diaphragms were excised after a 30-min in vivo exposure at birth, 24, 48, 72, or 168 hr of age and in the adult rats. Insulin increased net incorporation of radiolabeled glucose into diaphragm glycogen in comparison to age-matched controls (p < 0.025). The percent stimulation by insulin of labeled glucose into diaphragm glycogen was low at birth (250%) and at 24 hr (200%), but increased with advancing age and approached adult levels by 168 hr (1270%). At birth and at 24 hr, a 5-log insulin dose-response curve showed significant net incorporation only at 5000 μU insulin/g rat pup weight; by 72 hr a significant increase was noted at 50 μU insulin/g rat pup weight. Muscle glycogen concentration was high at birth ($\text{1.22 mg}\text{100 mg tissue}$), fell to 50% of the birth value from 24 through 168 hr, and could not account for the decreased insulin response noted. Decreased uptake of deoxyglucose into diaphragm in vivo paralleled the reduced net incorporation of radiolabeled glucose into diaphragm glycogen during the time period studied. The data are interpreted to indicate a blunted responsiveness of skeletal muscle to insulin during the first 48 hr in rats, which is related to decreased sensitivity of hexose transport to insulin.     

Roles of adipose restriction and metabolic factors in progression of steatosis to steatohepatitis in obese, diabetic mice

Background and Aims: We previously reported that steatohepatitis develops in obese, hypercholesterolemic, diabetic foz/foz mice fed a high‐fat (HF) diet for 12 months. We now report earlier onset of steatohepatitis in relation to metabolic abnormalities, and clarify the roles of dietary fat and bodily lipid partitioning on steatosis severity, liver injury and inflammatory recruitment in this novel non‐alcoholic steatohepatitis (NASH) model. Methods: Foz/foz (Alms1 mutant) and wild‐type (WT) mice were fed a HF diet or chow, and metabolic characteristics and liver histology were studied at 2, 6, 12 and 24 weeks. Results: After 12 weeks HF‐feeding, foz/foz mice were obese and diabetic with approximately 70% reduction in serum adiponectin. Hepatomegaly developed at this time, corresponding to a plateau in adipose expansion and increased adipose inflammation. Liver histology showed mild inflammation and hepatocyte ballooning as well as steatosis. By 24 weeks, HF‐fed foz/foz mice developed severe steatohepatitis (marked steatosis, alanine aminotransferase elevation, ballooning, inflammation, fibrosis), whereas dietary and genetic controls showed only simple steatosis. While steatosis was associated with hepatic lipogenesis, indicated by increased fatty acid synthase activity, steatohepatitis was associated with significantly higher levels of CD36, indicating active fatty acid uptake, possibly under the influence of peroxisome proliferator‐activated receptor‐γ. Conclusion: In mice genetically predisposed to obesity and diabetes, HF feeding leads to restriction of adipose tissue for accommodation of excess energy, causing lipid partitioning into liver, and transformation of simple steatosis to fibrosing steatohepatitis. The way in which HF feeding ‘saturates’ adipose stores, decreases serum adiponectin and causes hepatic inflammation in steatohepatitis may provide clues to pathogenesis of NASH in metabolic syndrome.     

Effects of starvation, refeeding, and insulin on energy-linked metabolic processes in catfish (Rhamdia hilarii) adapted to a carbohydrate-rich diet

The effects of starvation and of a short period of refeeding on energy-linked metabolic processes, as well as the effects of insulin administration, were investigated in an omnivorous fish (catfish, Rhamdia hilarii) previously adapted to a carbohydrate-rich diet. Following food deprivation blood sugar levels declined progressively to about 50% of fed values after 30 days. During the same period plasma free fatty acid (FFA) concentration increased twofold. Starvation resulted in reduced concentrations of lipid and glycogen in the liver and of glycogen, lipid, and protein in white muscle. However, taking into account the initial and final concentrations of tissue constituents, the liver weight, and the large fractions of body weight represented by muscle, it could be estimated that most of the energy utilized during starvation derived from the catabolism of muscle lipid and protein. Refeeding starved fishes for 48 hr induced several-fold increases in the rates of in vivo and in vitro incorporation of [14C]glucose into liver and muscle lipid and of [14C]glycine into liver and muscle protein. Incorporation of [14C]glucose into liver glycogen was also increased. However; refeeding did not affect the incorporation of labeled glucose into muscle glycogen, neither in vivo nor in vitro. Administration of pharmacological doses of insulin to normally fed catfishes resulted in marked increases in the in vivo incorporation of 14C from glucose into lipid and protein in both liver and muscle. In contrast, labeled glucose incorporation into muscle glycogen was not affected by insulin and label incorporation into liver glycogen was actually lower than that in noninjected controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of caloric restriction on basal insulin levels and the in vivo lipogenesis and glycogen synthesis from glucose in the Koletsky obese rat

Fasting plasma immunoreactive insulin levels increased with age in hyperinsulinemic Koletsky obese rats, being almost four times as high as in lean siblings at 3 mo (40 ± 5 μU/ml) and rising steadily to 82 ± 4 μU/ml at 6 mo (about seven times higher than lean siblings). Restricting the food intake of the obese rats markedly reduced but did not normalize the hyperinsulinemia, which in these rats was accompanied by normal plasma glucose concentrations. The incorporation in vivo of D-U-¹⁴C-glucose into tissue lipids and glycogen was measured 1 hr after the intravenous injection of 1 g glucose (containing 100 μCi D-U-¹⁴C-glucose) per kg body weight in obese rats eating ad libitum, obese rats after 3 mo on a restricted food intake, and lean siblings. All tissues (heart, diaphragm, skeletal muscle, and adipose tissues and liver) of obese rats exhibited a significantly greater lipogenesis from glucose than those of lean siblings. Dietary restriction of the obese rats reduced the ¹⁴C incorporation into lipid to levels not significantly different from lean controls in all tissues except skeletal muscle and liver, where, although greatly reduced, lipogenesis was still significantly higher than in lean rats. Glycogen synthesis tended to be greater in all tissues of obese rats than in lean animals. Dietary restriction of obese rats did not greatly affect glycogen synthesis.     

Metformin action on lipid metabolism in lesions of experimental aortic atherosclerosis of rabbits

The aim of the present study was to investigate whether metformin was capable of altering aortic lipid metabolism during the progression and regression of cholesterol-induced atherosclerosis in rabbits. Three hours after intravenous injection of a 200-microCi tracer dose of [2-14C]acetate, metformin (120 mg/kg per os) strongly diminished the radioactivity in all lipid fractions of the aorta of the normal rabbit. The incorporation of acetate into lipids was greater in the fatty streaks of rabbits fed cholesterol for 2 months than in normal aorta, independent of the plasma radioactivity level. There was increased acetate incorporation into all major lipid groups in the fatty streak, with the greatest relative increase in the cholesteryl ester fraction. No change was observed in the acetate incorporation into lipids in atheromatous deposits after pretreatment of cholesterol-fed rabbits for 8 days with metformin. Concomitant treatment for 2 months with metformin in rabbits fed a cholesterol-enriched diet strongly reduced the radioactivity of total aortic lipids 3 h after intravenous injection of labelled acetate. The inhibition of acetate incorporation into arterial lipids was observed in all lipid fractions (i.e. free cholesterol, free fatty acids, triglycerides and especially esterified cholesterol and phospholipids). In rabbits fed a cholesterol-enriched diet for a period of two months, followed by a normal diet during 12 months, long-term treatment with metformin significantly reduced total lipid radioactivity in the aorta, 3 h after intravenous injection of the 200-microCi tracer dose of [2-14C]acetate. The incorporation of labelled precursor was markedly reduced in the various lipid fractions. These properties, added to others previously described, can to a large extent explain the protective effect of metformin on experimental atherosclerosis.     

Regulation of cholesterol synthesis in jejunal absorptive cells of the rat

Cholesterol metabolism was studied in jejunal mucosa of the rat with special emphasis on cholesterol synthesis of villous cells, the site of intestinal lipid absorption. The type of diet and nutritional state clearly affected the cholesterologenesis of villous cells. Consequently, the incorporation of 14C-acetate into nonsaponifiable lipids (NSL; includes squalene and sterols) decreased in the following order of magnitude: 1) fat-free diet supplemented with safflower oil (FFD-SO), 2) FFD alone, 3) standard rat chow, 4) 1% cholesterol in FFD-S(, 5) total fast. Both the cholesterol feeding and the fast increased the total cholesterol concentrations in the villous cells, but the concentrations were unaffected by the other diets. In rats fed FFD-SO diet the cholesterol synthesis was significantly higher in the villous than in the crypt cells, although the cellular cholesterol concentrations were similar. The hepatic cholesterol synthesis from 14C-acetate was low in rats fed FFD-SO as compared with chow diet, whereas the incorporation of 14C-acetate into hepatic fatty acids and the incorporation of 3H-mevalonate into NSL were not affected by the diet. 5% cholestyramine had no significant effect on the cholesterol synthesis or cholesterol concentrations of the villous cells during high (FFD-SO diet) or low cholesterol synthesis (chow or cholesterol feeding). FFD-SO increased serum total cholesterol compared with chow diet and total fast, whereas cholestyramine and cholesterol feeding had no effect. Intraperitoneal administration of the hypocholesterolemic agent, 4-aminopyrazolopyrimidine, to fasting rats decreased markedly crypt cell cholesterol and increased cholesterol synthesis in the crypt cells and in the villous cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucose and fatty acid kinetics in fasted rats: Effects of previous protein intake

Glucose and fatty acid turnover and oxidation were measured in 48 hr fasted adult rats who had been previously fed two isocaloric diets of 5% and 18% protein content for 29 days. Kinetics were investigated with the simultaneous primed constant infusions of 6-³H glucose, U-¹⁴C glucose and 1-¹³C palmitic acid. Plasma glucose concentration and glucose turnover were reduced while plasma fatty acid concentration and turnover were increased in the rats fed the 5% protein diet. The protein:carbohydrate ratio of a previous diet affects both glucose and lipid metabolism in adult rats who are fasted.     

In vitro glucose metabolism and lipid biosynthesis in bovine ventricular valves

In vitro oxygen uptake, pathways of [U-¹⁴C] glucose degradation and lipogenesis in the mitral and tricuspid valve of normal bovine heart were compared. In the mitral valve the oxygen consumption, ATP/ADP ratio, lipid content and the amounts of [¹⁴C]-glucose and [¹⁴C]-acetate incorporated into total lipids per mg DNA were higher, while lactate production and NADH/NAD ratio were lower, than those found in tricuspid valve. Triglycerides and phospholipids represented the largest lipid fractions in the mitral and tricuspid valve, respectively, and contained about 60% of the radioactivity incorporated into total lipids, but the highest relative rate of synthesis in the mitral and tricuspid valve was calculated to be for phospholipids and triglycerides, respectively. The bulk (94 to 98%) of [¹⁴C]-glucose incorprated into phospholipids and triglycerides by ventricular valves was found in the glycerol moiety. Incorporation of [¹⁴C]-glucose into fatty acids was markedly lower in the tricuspid than in the mitral valve. In the mitral valve the synthesis of 16 : 0 fatty acid from [I-¹⁴C] acetate proceeded de novo while in the tricuspid valve by a combination of de novo synthesis and chain elongation.     

Despite transient ketosis, the classic high-fat ketogenic diet induces marked changes in fatty acid metabolism in rats

In contrast to humans, rats on a high-fat ketogenic diet seem incapable of maintaining plasma beta-hydroxybutyrate above 1 mmol/L for more than a week. Our goal was to determine whether fatty acid metabolism in rats changes despite the absence of sustained ketosis induced by the ketogenic diet. Fatty acid metabolism was assessed as changes in tissue fatty acid profiles and change in 13C-alpha-linolenic acid incorporation into plasma, liver, adipose tissue, and brain lipids. Despite loss of ketosis, the ketogenic diet reduced some polyunsaturated fatty acids in adipose tissue (up to 44%) and plasma (up to 90%) but raised polyunsaturates in liver triglycerides by up to 25-fold and raised arachidonic and docosahexaenoic acids in the brain by 15%. Lower tissue incorporation of 13C-alpha-linolenic acid but higher unlabeled and 13C-labeled docosahexaenoic acid in brain supports the view that the principal changes in fatty acid composition resulted from enhanced mobilization of polyunsaturates from adipose tissue to liver and brain. In the absence of sustained ketosis, changes in fatty acid metabolism resulting in an increase in brain polyunsaturates, particularly docosahexaenoic acid may, nevertheless, contribute to the seizure protection by the ketogenic diet.     

Glycolytic and lipolytic effects of ovine FSH and estradiol-17 in the lizard Anolis carolinensis

The effects of estradiol-17β and FSH on the abdominal fat bodies, liver glycogen and lipid stores, and plasma glucose levels were investigated in vitellogenic and nonvitellogenic Anolis carolinensis. In vitellogenic (April) lizards, the administration of estradiol significantly reduced liver glycogen levels and both the weight and the lipid content of the fat bodies; liver weight and lipid content were not affected. Estradiol treatment had no effect upon the incorporation of ¹⁴C from an injected glucose load into hepatic glycogen or lipid, but reduced the amount of label incorporated into fat body lipid.In non-vitellogenic lizards, both estradiol and FSH elicited similar responses in carbohydrate and lipid stores. Both hormones reduced liver glycogen and plasma glucose levels, but did not significantly affect abdominal fat body weights or liver lipid levels. Oviducal weights were increased in response to both hormones, but an increase in ovarian weight was observed only after FSH treatment.     

Incorporation of orally administered glucose-U-14C and fructose-U-14C into the triglyceride of liver, plasma, and adipose tissue of rats

Male rats, fasted for 5–6 hr, were given glucose-U-¹⁴C or fructose-U-¹⁴C, with their respective carrier, by intragastric instillation. Sequential radioactivity in plasma carbohydrates and in the triglyceride of the liver, plasma, and adipose tissue and plasma immunoreactive insulin and free fatty acids were measured. The validity of taking the triglyceride labeling rate as the triglyceride synthesis rate was tested by measuring the metabolic activity of endogenous glucose. Two or three times greater radioactivity was found in the liver and plasma triglycerides after fructose than after glucose while the reverse was true for adipose tissue. The greater radioactivity in triglyceride of the liver and plasma after fructose was mainly due to triglyceride-glycerol radioactivity. The greater radioactivity in adipose tissue triglyceride was due to the radioactivity of both triglyceride-fatty acids and triglyceride-glycerol. Three hours after glucose, 92% of the total radioactivity in triglyceride was in adipose tissue and 8% was in the liver. However, 3 hr after fructose, 57% of the radioactivity was in adipose tissue and 42% was in the liver. Daily repetition of such a pattern of fructose handling may lead to abnormal metabolism of endogenous triglyceride.     

Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients

Aims/hypothesis In the present study, we investigated the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use in type 2 diabetic patients.Materials and methods We studied ten type 2 diabetic patients under the following conditions: (1) at rest; (2) during 60 min of cycling exercise at 50% of maximal workload capacity and subsequent recovery. Studies were done under normal, fasting conditions (control trial: CON) and following administration of a nicotinic acid analogue (low plasma non-esterified fatty acid trial: LFA). Continuous [U-¹³C]palmitate and [6,6 -²H₂]glucose infusions were applied to quantify plasma NEFA and glucose oxidation rates, and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in lipid and glycogen content specific to muscle fibre type.Results Following administration of the nicotinic acid analogue (Acipimox), the plasma NEFA rate of appearance was effectively reduced, resulting in lower NEFA concentrations in the LFA trial (p<0.001). Plasma NEFA oxidation rates were substantially reduced at rest, during exercise and subsequent recovery in the LFA trial. The lower plasma NEFA oxidation rates were compensated by an increase in IMTG and endogenous carbohydrate use (p<0.05). Plasma glucose disposal rates did not differ between trials. In accordance with the tracer data, a greater net decline in type I muscle fibre lipid content was observed following exercise in the LFA trial (p<0.05).Conclusions/interpretation This study shows that plasma NEFA availability regulates IMTG use, and that adipose tissue lipolytic inhibition, in combination with exercise, could be an effective means of augmenting intramuscular lipid and glycogen use in type 2 diabetic patients in an overnight fasted state.     

Transfer of [1(-14)C] palmitate between myocardial cell fractions.

Mitochondrial, microsomal and cytoplasmic fractions from the heart, labelled with [1-¹⁴C] palmitate, have been added to non-radioactive myocardial homogenate and the distribution of lipid radio-activity between the three cell fractions determined. During the course of rehomogenisation and cell fractionation at 4°C a substantial movement of lipid radioactivity occurred between all three fractions. Expressed as lipid radioactivity/mg protein the activity of the microsomal fraction was greatest. This appears to be due to the rapid incorporation of radioactive fatty acid into phospholipid in the microsomal fraction.After perfusion of isolated rat hearts with [1-¹⁴C] palmitate complexed to albumin for 15 s at 4°C over 90% of the radioactivity of the mitochondrial and cytoplasmic fractions was present in free fatty acids. This figure was significantly lower in the microsomal fraction where some 15% of the radioactivity was already present in phospholipid.Washing mitochondrial and microsomal fractions with albumin solution removed more lipid radioactivity than washing with sucrose solution and removed a greater proportion of radioactivity from free fatty acids than from phospholipid.It is concluded that during perfusion or during cell-fractionation at 4°C free fatty acids transfer rapidly between subcellular components. The rapid incorporation of radioactive fatty acids into phospholipid in the microsomal fraction decreases the mobility of label from this fraction.     

Serum insulin and lipogenesis in the suckling ‘fatty’ fa/fa rat

Summary Preobese fatty fa/fa rats identified by their decreased rectal temperature were either given access to high carbohydrate chow or maintained on a suckling only diet till 20 days of age. Serum insulin, hepatic and adipose tissue fatty acid synthesis and lipogenic enzyme activities were low in suckling preobese fa/fa. In animals with access to chow diet, hepatic lipogenesis was unaltered, serum insulin rose to similar levels in lean and preobese fa/fa (lean 62±5; preobese 69±4 U/ml), but adipose tissue lipogenesis was increased to higher levels in the preobese than lean rats (lean 0.56±0.12; preobese 1.80±0.22 mol. tissue^-1. h^-1). The activities of glucose-6-phosphate dehydrogenase, acetyl coenzyme A carboxylase and fatty acid synthetase were increased in adipose tissue of preobese fa/fa rats. Neither streptozotocin treatment nor pretreatment with Triton WR 1339 abolished the difference in adipose tissue lipogenesis between lean and preobese fa/fa rats. Preobese fa/fa rats showed an enhanced insulin secretory response to a glucose load.     

Endogenous glucose production, gluconeogenesis and liver glycogen concentration in obese non-diabetic patients

Summary Resting, post-absorptive endogenous glucose production (EGP), fractional gluconeogenesis and liver glycogen concentration were assessed in 6 lean and 5 obese non-diabetic subjects undergoing elective abdominal surgery. During the 2 days preceding these measurements, 0.3 g/day U-¹³C glucose had been added to their usual diet to label their endogenous glycogen stores. On the morning of day 3, EGP was measured with 6,6-²H glucose. Their endogenous ¹³C glycogen enrichment was calculated from ¹³CO₂ and respiratory gas exchanges. Fractional gluconeogenesis was assessed as 1-(¹³C glucose/¹³C glycogen) · 100. EGP was similar in lean subjects (113 ± 5 mg/min) and in obese subjects (111 ± 6). Fractional gluconeogenesis was higher in obese (59 ± 10 %) than in lean subjects (29 ± 8 %). However, overall EGP remained constant due to a decrease in glycogenolysis. Since an increased gluconeogenesis and a decreased glycogenolysis may both contribute to increase liver glycogen concentration in obesity, hepatic glycogen concentrations were assessed in hepatic needle biopsies obtained during surgery. Hepatic glycogen concentrations were increased in obese patients (515 ± 38 mg/g protein) compared to lean subjects (308 ± 58, p < 0.05). It is concluded that in obese patients: a) fractional gluconeogenesis is increased; b) overall EGP is unchanged due to a proportional inhibition of glycogenolysis; c) liver glycogen concentration is increased. [Diabetologia (1997) 40: 463–468] Received: 10 April 1996 and in final revised form: 31 December 1996