Changes in UCP expression in tissues of Zucker rats fed diets with different protein content

The effect of dietary protein content on the uncoupling proteins (UCP) 1, 2 and 3 expression in a number of tissues of Zucker lean and obese rats was studied. Thirty-day-old male Zucker lean (Fa/?) and obese (fa/fa) rats were fed on hyperproteic (HP, 30% protein), standard (RD, 17% protein) or hypoproteic (LP, 9% protein) diets ad libitum for 30 days. Although dietary protein intake affected the weights of individual muscles in lean and obese animals, these weights were similar. In contrast, huge differences were observed in brown adipose tissue (BAT) and liver weights. Lean rats fed on the LP diet generally increased UCP expression, whereas the HP group had lower values. Obese animals, HP and LP groups showed higher UCP expression in muscles, with slight differences in BAT and lower values for UCP3 in subcutaneous adipose tissue. The mean values of UCP expression in BAT of obese rats were lower than in their lean counterpart, whereas the expression in skeletal muscle was increased. Thus, expression of UCPs can be modified by dietary protein content, in lean and obese rats. A possible thermogenic function of UCP3 in muscle and WAT in obese rats must be taken into account.     

The level of dietary protein and carbohydrate has a different effect on intestinal uptake of hexoses and lipids in rabbits with an ileal resection than in those with an intact intestinal tract

Either high protein, low carbohydrate (HP) or low protein, high carbohydrate (LP) diets were fed for 6 weeks to rabbits with or without resection of the distal half of the small intestine. Control and resected rabbits fed HP consumed more food and gained more weight than the animals fed LP. The level of dietary protein has a different effect on intestinal transport in animals with an ileal resection than in those with an intact small intestine. With 0.5 mM glucose, the in vitro uptake in control rabbits was greater for the LP than HP diet but was unchanged in resected rabbits; uptake of 0.5 mM galactose and 3-O-methyl glucose was unaffected by HP and LP, whereas in rabbit uptake was lower in LP than HP. The uptake of 40 mM glucose was greater with the LP than HP diet in control rabbits, but lower with LP than HP in resected rabbits. In control rabbits, the uptake of aluric acid was lower on the LP than HP diet; the uptake of octanoic acid, decanoic acid, and cholesterol was unchanged; and the uptake of each fatty acid and cholesterol was greater in resected rabbits fed LP than HP. Feeding a low protein diet to animals with an ileal resection is associated with lower jejunal uptake of high concentrations of glucose, but the higher uptake of galactose and enhanced permeability to fatty acids result in superior weight gain. Thus, recommendations for alterations in dietary protein and carbohydrate levels following ileal resection must be made with the knowledge that these changes may influence intestinal transport function as well as body weight gain.     

Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men

While protein is regarded as the most satiating macronutrient, many studies have employed test meals that had very high and unsustainable protein contents. Furthermore, the comparative responses between lean and obese subjects and the relationships between energy intake suppression and gut hormone release remain unclear. We evaluated the acute effects of meals with modest variations in 1) fat, protein, and carbohydrate content and 2) protein load on gastrointestinal hormones, appetite, and subsequent energy intake in lean and obese subjects. Sixteen lean and sixteen obese men were studied on four occasions. Following a standardized breakfast, they received for lunch: 1) high-fat (HF), 2) high-protein (HP), 3) high-carbohydrate/low-protein (HC/LP), or 4) adequate-protein (AP) isocaloric test meals. Hunger, fullness, and gut hormones were measured throughout, and at t = 180 min energy intake at a buffet meal was quantified. In lean subjects, hunger was less and fullness greater following HF, HP, and AP compared with HC/LP meals, and energy intake was less following HF and HP compared with HC meals (P < 0.05). In the obese subjects, hunger was less following HP compared with HF, HC/LP, and AP meals, and energy intake was less following HP and AP compared with HF and HC meals (P < 0.05). There were no major differences in hormone responses to the meals among subject groups, but the CCK and ghrelin responses to HP and AP were sustained in both groups. In conclusion, HP meals suppress energy intake in lean and obese subjects, an effect potentially mediated by CCK and ghrelin, while obese individuals appear to be less sensitive to the satiating effects of fat.     

Splanchnic amino acid pattern in genetic and dietary obesity in the rat

The study of intestinal and hepatic uptake of amino acids by obese rats has been the main objective of this work. The obese animals used were either from genetic or from nutritional basis. In fed state, the intestinal release of amino acids was higher in obese animals than in lean ones (around the double values), but nutritionally and genetically obese rat showed a related pattern, specially for the case of alanine (increased release in relation to controls by a factor of 10). The higher alanine release by intestine is not reversed by 12-h food deprivation. The hepatic availability was also higher in obesity models than in lean animals (increases over 30%). However, the hepatic uptake was increased in genetically obese animals (more than 35%) and decreased in nutritionally obese animals (more than 40%), especially due to alanine uptake(2419, 1100 and 3794 nmols/min/g protein in lean, Diet-ob andfa/fa animals respectively). In obese animals the food deprivation tended to normalize the hepatic uptake of alanine. The differences in alanine uptake between both types of obesity may reflect the differences of urea synthesis.     

Effect of undegradable protein supply on testicular size, spermiogram parameters and sexual behavior of mature Assaf rams

Eighteen mature Assaf rams were used to study the effect of undegradable protein (UDP) supply on testicular size, sperm production and quality, testosterone secretion and reproductive behavior. Animals were allocated to three groups of six animals each and fed during 10 weeks with different diets which were designed to supply approximately 0.5MJ of metabolisable energy (ME)/kg LBW(0.75) and 9g of effective rumen degradable protein (ERDP)/MJ of fermentable ME to all animals and to induce differences in rumen UDP intake (0.97, 1.72 and 3.08g of UDP/kg LBW(0.75) for LP, MP and HP diets, respectively). Neither plasma testosterone concentration nor reproductive behavior parameters (number of services, number of mounts without ejaculation and reaction time to first mount) were affected (P > 0.05) by protein intake. Nevertheless, there were significant (P < 0.05) differences between diets in both testicular size and sperm production. Scrotal circumference was lower in LP compared to MP and HP groups, no significant differences being observed between these latter two groups at any time. In relation to sperm production, the lowest and the highest values were always observed in LP and HP groups, respectively. MP group showed intermediate values, significantly different from those of LP and HP groups on Week 5 and only from those of LP group on Week 9. The present results provide a better understanding of the effect of protein nutrition and suggest that UDP should be supplied to Assaf rams during the mating season to improve their reproductive performance.     

Absorption of a protein gavage in Zucker lean rats. Influence of protein content in the diet.

The rate of protein absorption was measured in Zucker lean rats. Rats were fed with a bolus that contained ca. 300 mg of 14C-labelled protein at the beginning of the light cycle. Blood was extracted from the portal vein at intervals up to 9 hours after gavage. Label incorporation into tissue protein was monitored. The digestion and absorption of protein was slow, and 9 hours after the gavage, 20% of the bolus remained in the stomach. Forty percent of the protein was absorbed in the first hour. This was followed first by a linear absorption process, then by the amino acid incorporation into tissue proteins. The appearance of label in the portal vein increased progressively for up to four hours, shifting to a progressive decrease that coincides with the maintenance of this label in the tissues. The skin, the striated muscle and the liver showed the highest amounts of labelled proteins. The application of this model to animals fed low-(LP) or high-protein (HP) content diets showed that the HP group digested the protein faster than the LP group, and that catabolism of the amino acids was higher in the HP group. The LP group digested protein much more slowly than the RD (control) group, but protein accretion was more efficient.     

Proposed mechanism for increased insulin-mediated glucose transport in adipose cells from young, obese Zucker rats. Large intracellular pool of glucose transporters

The mechanism for hyperresponsive insulin-mediated glucose transport in adipose cells from 30-day-old obese Zucker rats was examined. Glucose transport was assayed by measuring 3-O-methylglucose transport, and the concentration of glucose transporters was estimated by measuring specific D-glucose-inhibitable cytochalasin B binding. Insulin increased glucose transport activity by approximately 17 fmol/cell/min in cells from obese rats compared to 3 fmol/cell/min in lean littermates. Insulin increased the concentration of glucose transporters in the plasma membrane fraction by about 15 pmol/mg of membrane protein in both groups. The insulin-mediated decrease in the concentration of transporters in the low-density microsomal fraction was 30 pmol/mg of membrane protein for the obese rats compared to 15 pmol/mg of membrane protein for the lean controls. An estimated number of glucose transporters was calculated using membrane protein and enzyme recoveries for each group. Insulin increased the number of transporters in the plasma membrane by 3 X 10(6) sites/cell for the obese rats and only 0.6 X 10(6) sites/cell for the lean controls. In addition, insulin decreased the number of transporters/cell in the intracellular membrane pool by approximately 4 X 10(6) sites/cell for the obese rats and 0.9 X 10(6) sites/cells for the lean rats. The total number of transporters/cell was about 7 X 10(6) sites/cell for the obese animals and 1.6 X 10(6) sites/cell for the lean controls. In the basal state, more than 80% of these transporters were located in the intracellular pool for both the lean and obese rats. Thus, the marked hyperresponsive insulin-mediated glucose transport observed in adipose cells from 30-day-old obese Zucker rats may be the consequence of a marked increase in the number of glucose transporters in the intracellular pool.     

Ammonium uptake and urea production in hepatocytes from lean and obese Zucker rats

The metabolic differences in vitro between genetic and dietary obese rats in the uptake of ammonium and amino acids by the liver and their use for ureogenesis have been assayed using hepatocytes isolated from Lean, Obese Zucker (Genetic obese) rats and Dietary obese rats. The hepatocytes of genetic obese animals took up more ammonium and produced higher amounts of urea from ammonium and alanine than those of lean and dietary obese groups (2 and 5 times more respectively). In the lean and dietary obese groups urea synthesis accounted for almost all the nitrogen taken up as ammonium. Thus, dietary and genetic obesity show a widely different handling of nitrogen, and the genetic obese rats need to break down protein to maintain their hepatocyte function.     

Dehydroepiandrosterone alters Zucker rat soleus and cardiac muscle lipid profiles

High levels of serum free fatty acids (FFA) and lower proportions of polyunsaturated (PU) FAs, specifically arachidonic acid (AA), are common in obesity, insulin resistance (IR), and type 2 diabetes mellitus. Dehydrepiandrosterone (DHEA) decreases body fat content, dietary fat consumption, and insulin levels in obese Zucker rats (ZR), a genetic model of human youth onset obesity and type 2 diabetes. This study was conducted to investigate DHEA's effects on lean and obese ZR serum FFA levels and total lipid (TL) FA profiles in heart and soleus muscle. We postulated that DHEA alters serum FFA levels and tissue TL FA profiles of obese ZR so that they resemble the levels and profiles of lean ZR. If so, DHEA may directly or indirectly alter tissue lipids, FFA flux, and perhaps lower IR in obese ZR. Lean and obese male ZR were divided into six groups with 10 animals in each: obese ad libitum control, obese pair-fed, obese DHEA, lean ad libitum control, lean pair-fed, and lean DHEA. All animals had ad libitum access to a diet whose calories were 50% fat, 30% carbohydrate, and 20% protein. Only the diets of the DHEA treatment groups were supplemented with 0.6% DHEA. Pair-fed groups were given the average number of calories per day consumed by their corresponding DHEA group, and ad libitum groups had 24-h access to the DHEA-free diet. Serum FFA levels and heart and soleus TL FA profiles were measured. Serum FFA levels were higher in obese (approximately 1 mmol/L) compared to lean (approximately 0.6 mmol/L) ZR, regardless of group. In hearts, monounsaturated (MU) FA were greater and PU FA were proportionally lower in obese compared to the lean rats. In soleus, saturated and MU FA were greater and PU FA were proportionally lower in the obese compared to the lean rats. DHEA groups displayed significantly increased proportions of TL AA and decreased oleic acid in both muscle types. Mechanisms by which DHEA alters TL FA profiles are a reflection of changes occurring within specific lipid fractions such as FFA, phospholipid, and triglyceride. This study provides initial insights into DHEA's lipid altering effects.     

Insulin-stimulated glucose transport in muscle. Evidence for a protein-kinase-C-dependent component which is unaltered in insulin-resistant mice.

The aim of our work was to investigate a possible role of protein kinase C (PKC) in insulin-stimulated glucose uptake in mouse skeletal muscle, and to search for a defect in PKC activation in insulin resistance found in obesity. In isolated soleus muscle of lean mice, insulin (100 nM) and 12-O-tetradecanoylphorbol 13-acetate (TPA) (1 microM) acutely stimulated glucose uptake 3- and 2-fold respectively. The effects of insulin and TPA were not additive. When PKC activity was down-regulated by long-term (24 h) TPA pretreatment, before measurement of glucose transport, the TPA effect was abolished, but in addition insulin-stimulated glucose transport returned to basal values. Furthermore, polymyxin B, which inhibits PKC in muscle extracts, prevented insulin-stimulated glucose uptake in muscle. In muscle of obese insulin-resistant mice, glucose uptake evoked by insulin was decreased, whereas the TPA effect, expressed as a fold increase, was unaltered. Thus both agents stimulated glucose transport to the same extent. Furthermore, no difference was observed when PKC activation by TPA was measured in muscle from lean and obese mice. These results suggest that: (1) PKC is involved in the insulin effect on glucose transport in muscle; (2) PKC activation explains only part of the insulin stimulation of glucose transport; (3) the defect in insulin response in obese mice does not appear to be due to an alteration in the PKC-dependent component of glucose transport. We propose that insulin stimulation of glucose uptake occurs by a sequential two-step mechanism, with first translocation of transporters to the plasma membrane, which is PKC dependent, and second, activation of the glucose transporters. In obesity only the activation step was decreased, whereas the translocation step was unaltered.     

Effect of lithium on hepatic and serum elemental status under different dietary protein regimens

Lithium carbonate at the dose level of 1.1 g/kg was administered in diet to normal (18% protein), low-protein-(LP; 8%) and highprotein (HP; 30% diet)-fed rats for a period of 1 mo. The LP diet resulted in a significant decrease in the hepatic levels of zinc, iron, copper, manganese, calcium, and serum levels of calcium and sodium. The HP diet caused a marked decrease in copper and calcium levels in liver, but an increase in potassium levels in serum was observed. Lithium treatment to normal rats led to a significant reduction in the hepatic contents of zinc, copper, potassium, calcium, and serum contents of potassium and sodium, whereas an elevation in serum contents of calcium was noticed. Administration of lithium to protein-deficient rats increased the hepatic concentration of manganese and serum concentration of calcium and the levels almost reached the normal limits. On the other hand, there was a marked depression in potassium contents in the serum of LP-as well as HP-fed rats following lithium treatment when compared to LP and HP groups, respectively.     

Effect of undegradable protein concentration in the post-weaning diet on body growth and reproductive development of Assaf rams

Twenty-four growing Assaf lambs, divided into four groups of six animals, were used to study the effect of the undegradable protein content of the post-weaning diet on feed intake, body growth and reproductive development. From week 1 to week 21, the four groups were fed ad libitum as follows: group LL was given barley straw and low protein concentrate (LP); group HH was given barley straw and high protein concentrate (HP); group LH was given barley straw and LP concentrate from week 1 to 11 (period 1) and barley straw and HP concentrate from week 12 to 21 (period 2); group HL was given barley straw and HP concentrate in period 1 and barley straw and LP concentrate in period 2. From week 22 to week 26 (period 3), all animals received the same amount of hay and LP concentrate. Barley straw intake was not significantly (P>0.05) affected by dietary treatments. In the 1st period, average concentrate intake and live body weight gain (LWG) were greater in lambs fed HP than LP supplement. In the 2nd period, concentrate intake was not significantly (P>0.05) affected by type of supplement, but LWG was greater for lambs fed HP than LP supplement. Scrotal circumference in week 11 was significantly (P<0.05) lower in lambs fed LP supplement than in lambs fed HP supplement. No significant differences (P>0.05) due to dietary treatments were observed on scrotal circumference in weeks 21 and 25. Dietary treatments had no significant (P>0.05) effect on either circulating concentration of testosterone or ejaculate characteristics. In conclusion, results from this study suggest that supplementing diets with undegradable protein enhanced performance throughout the breeding period and accelerated testis growth. Nevertheless, final testis size, pattern of circulating testosterone and sperm output were unaffected by dietary treatments.     

Interactive Effects of Indigestible Carbohydrates,Protein Type,and Protein Level on Biomarkers of Large Intestine Health in Rats

The effects of indigestible carbohydrates, protein type, and protein level on large intestine health were examined in rats. For 21 days, 12 groups of six 12-week-old male Wistar rats were fed diets with casein (CAS), or potato protein concentrate (PPC), providing 14% (lower protein level; LP), or 20% (higher protein level; HP) protein, and containing cellulose, resistant potato starch, or pectin. Fermentation end-products, pH, and β-glucuronidase levels in cecal digesta, and ammonia levels in colonic digesta were determined. Cecal digesta, tissue weights, cecal and colon morphology, and colonocyte DNA damage were also analyzed. Digesta pH was lower, whereas relative mass of cecal tissue and digesta were higher in rats fed pectin diets than in those fed cellulose. Cecal parameters were greater in rats fed PPC and HP diets than in those fed CAS and LP diets, respectively. Short-chain fatty acid (SCFA) concentrations were unaffected by protein or carbohydrate type. Total SCFA, acetic acid, and propionic acid concentrations were greater in rats fed LP diets than in those fed HP. Cecal pool of isobutyric and isovaleric acids was greater in rats fed PPC than in those fed CAS diets. PPC diets decreased phenol concentration and increased ammonia concentration in cecal and colonic digesta, respectively. Cecal crypt depth was greater in rats fed PPC and HP diets, and was unaffected by carbohydrates; whereas colonic crypt depth was greater in rats fed cellulose. Myenteron thickness in the cecum was unaffected by nutrition, but was greater in the colon of rats fed cellulose. Colonocyte DNA damage was greater in rats fed LP diets than in those fed HP diets, and was unaffected by carbohydrate or protein type. It was found that nutritional factors decreasing cecal digesta weight contribute to greater phenol production, increased DNA damage, and reduced ammonia concentration in the colon.     

Expression of rat liver Na+/L-alanine co-transport in Xenopus laevis oocytes. Effect of glucagon in vivo.

Poly(A)+ RNA (mRNA) isolated from rat liver was injected into Xenopus laevis oocytes, and expression of Na+/L-alanine transport was assayed by measuring Na(+)-dependent uptake of L-[3H]alanine. Expression of Na+/L-alanine transport was detected 3-7 days after mRNA injection, and was due to an increment of the Na(+)-dependent component. After injection of 40 ng of total mRNA, Na(+)-dependent uptake of L-alanine was 2.5-fold higher than in water-injected oocytes. In contrast with Na+/L-alanine transport by water-injected oocytes, expressed Na+/L-alanine transport was inhibited by N-methylaminoisobutyric acid, was inhibited by an extracellular pH of 6.5 and was saturated at approx. 1 mM-L-alanine. After sucrose-density-gradient fractionation, highest expression of Na+/L-alanine uptake was observed with mRNA of 1.9-2.5 kb in length. Compared with mRNA isolated from control rats, mRNA isolated from glucagon-treated rats showed a approx. 2-fold higher expression of Na+/L-alanine transport. The results demonstrate that both liver Na+/L-alanine transport systems (A and ASC) can be expressed in X. laevis oocytes. Furthermore, the data obtained with mRNA isolated from glucagon-treated rats suggest that glucagon regulates liver Na+/L-alanine transport (at least in part) via the availability of the corresponding mRNA.     

Divergent effects of rosiglitazone on protein-mediated fatty acid uptake in adipose and in muscle tissues of Zucker rats

Thiazolidinediones (TZDs) increase tissue insulin sensitivity in diabetes. Here, we hypothesize that, in adipose tissue, skeletal muscle, and heart, alterations in protein-mediated FA uptake are involved in the effect of TZDs. As a model, we used obese Zucker rats, orally treated for 16 days with 5 mg rosiglitazone (Rgz)/kg body mass/day. In adipose tissue from Rgz-treated rats, FA uptake capacity increased by 2.0-fold, coinciding with increased total contents of fatty acid translocase (FAT/CD36; 2.3-fold) and fatty acid transport protein 1 (1.7-fold) but not of plasmalemmal fatty acid binding protein, whereas only the plasmalemmal content of FAT/CD36 was changed (increase of 1.7-fold). The increase in FA uptake capacity of adipose tissue was associated with a decline in plasma FA and triacylglycerols (TAGs), suggesting that Rgz treatment enhanced plasma FA extraction by adipocytes. In obese hearts, Rgz treatment had no effect on the FA transport system, yet the total TAG content decreased, suggesting enhanced insulin sensitivity. Also, in skeletal muscle, the FA transport system was not changed. However, the TAG content remained unaltered in skeletal muscle, which coincided with increased cytoplasmic adipose-type FABP content, suggesting that increased extramyocellular TAGs mask the decline of intracellular TAG in muscle. In conclusion, our study implicates FAT/CD36 in the mechanism by which Rgz increases tissue insulin sensitivity.     

Development of system B0,+ and a broad-scope Na(+)-dependent transporter of zwitterionic amino acids in preimplantation mouse conceptuses

The nature and ontogeny of Na(+)-dependent L-alanine transport was examined in mouse eggs and preimplantation conceptuses. Mediated L-alanine uptake was not detected in fertilized or unfertilized eggs, but a small amount of Na(+)-dependent L-alanine transport was detected in 2-cell conceptuses. Na(+)-dependent alanine transport was more rapid at the 8-cell stage of development, and more than 10-fold faster in blastocysts than in 8-cell conceptuses. Analog inhibition analyses were consistent with the interpretation that L-lysine-sensitive and L-lysine-resistant components of transport were present at the 2-cell, 8-cell and blastocyst stages of development. The range of amino acids and their analogs that inhibited the most conspicuous component of alanine transport in blastocysts was consistent with the conclusion that system B0,+ is largely responsible for L-alanine uptake in these conceptuses. Moreover, system B0,+, but not other known systems in blastocysts, became susceptible to activation as these conceptuses approached the time of implantation, so this activation could be involved in implantation. Although the data are consistent with the possibility that system B0,+ is also present in 2-cell and 8-cell conceptuses, the relatively slow L-alanine transport in conceptuses at these earlier stages of development precluded more detailed study of their ability to take up alanine. Similarly, the less conspicuous L-lysine-resistant component of L-alanine transport in blastocysts also may be present in conceptuses as early as the 2-cell stage. The L-lysine-resistant component of L-alanine transport could not be attributed to residual system B0,+ activity, however, because it was inhibited more strongly by trans-OH-L-proline than L-arginine, whereas the reverse was the case for system B0,+. Similarly, L-tryptophan and L-leucine each inhibited system B0,+ more strongly than L-serine or L-cysteine, whereas all four of these amino acids inhibited the L-lysine-resistant component equally well. Moreover, a Hofstee plot for L-alanine influx was consistent with the interpretation that at least two mediated components of Na(+)-dependent L-alanine transport are present in blastocysts. The less conspicuous component of L-alanine transport in blastocysts was relatively susceptible to inhibition by L-leucine and L-tryptophan, but it resisted inhibition by the 'model' system A substrate, MeAIB, and the system ASC inhibitors, L-penicillamine and cationic amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)     

Insulin sensitivity, fat distribution, and adipocytokine response to different diets in lean and obese cats before and after weight loss

Obesity is a major health problem in cats and a risk factor for diabetes. It has been postulated that cats are always gluconeogenic and that the rise in obesity might be related to high dietary carbohydrates. We examined the effect of a high-carbohydrate/low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on glucose and fat metabolism during euglycemic hyperinsulinemic clamp, adipocytokines, and fat distribution in 12 lean and 16 obese cats before and after weight loss. Feeding diet HP led to greater heat production in lean but not in obese cats. Regardless of diet, obese cats had markedly decreased glucose effectiveness and insulin resistance, but greater suppression of nonesterified fatty acids during the euglycemic hyperinsulinemic clamp was seen in obese cats on diet HC compared with lean cats on either diet or obese cats on diet HP. In contrast to humans, obese cats had abdominal fat equally distributed subcutaneously and intra-abdominally. Weight loss normalized insulin sensitivity; however, increased nonesterified fatty acid suppression was maintained and fat loss was less in cats on diet HC. Adiponectin was negatively and leptin positively correlated with fat mass. Lean cats and cats during weight loss, but not obese cats, adapted to the varying dietary carbohydrate/protein content with changes in substrate oxidation. We conclude that diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats. These data also show that insulin sensitivity of glucose and fat metabolism can be differentially regulated in cats.     

Exercise training and the glucose transport system in obese SHHF/Mcc-facp rats

Ferrara, Cynthia M., W. Michael Sherman, Nicole Leenders,Sylvia A. McCune, and Karla Roehrig. Exercise training and theglucose transport system in obeseSHHF/Mcc-fa^cprats. J. Appl. Physiol. 81(4):1670-1676, 1996.The effects of a similar exercise trainingstimulus on maximal insulin-stimulated (MIS) plasma membrane glucosetransporter number and glucose transport were determined in lean andobeseSHHF/Mcc-fa^cprats. Six-week-old lean and obese male rats were randomly divided intofour groups: lean sedentary (LSed), obese sedentary (OSed), leanexercise (LEx), and obese exercise (OEx). An 8- to 12-wk treadmillrunning program equalized daily muscular work for LEx and OEx. Plasmamembranes were isolated from control and MIS muscles of mixed fibertypes. MIS significantly increased glucose transport (3.4- and2.8-fold) in LSed and OSed, respectively. MIS significantly increased glucose transporter number (2.5-fold) in LSed, but there wasno increase in glucose transporter number in OSed. Peak oxygen uptakeand citrate synthase activity were increased a similar amount for LExand OEx groups, demonstrating a similar training stimulus. MISsignificantly and similarly increased glucose transport in LEx and OEx(4.4- and 5.1-fold, respectively). The effects of MIS on plasmamembrane glucose transporter number in the exercise-trained rats weresimilar to the responses observed in the sedentary lean and obesegroups. MIS significantly increased glucose transporter number(2.6-fold) in LEx, whereas there was no increase in glucose transporternumber in OEx. The reduction in MIS glucose transport in OSed appearsto be related to a defect in the processes associated with thetranslocation of glucose transporters to the plasma membrane. Exercisetraining of the obese rats apparently did not alter this defect.Similar increases in peak oxygen uptake, citrate synthase, and MISglucose transport in LEx and OEx groups suggest that insulin resistancedoes not limit the ability of the glucose transport system to adapt toexercise training in the obese maleSHHF/Mcc-fa^cprats.

     

Non-shivering thermogenesis and obesity in adult diabetic Wistar fatty rats

1. Characteristics of resting and of norepinephrine (NE)-stimulated thermogenesis, and the glycemic response to NE were determined in adult male Wistar Fatty rats. Rats were maintained on Purina chow No. 5001 until 22 weeks of age, and fed semisynthetic diets containing 54% carbohydrate, 20% protein, 16% mixed fats, plus essential vitamins, minerals, and non-nutritive fiber from 22 until 30 weeks of age. 2. Obese rats were 50% heavier than lean throughout the study. Phenotype effects (obese greater than lean) were present for retroperitoneal (RP) and dorsal (DOR) white fat depot weight, adipocyte number per depot, and adipocyte lipid content. Epididymal mass and cellularity were similar in both phenotypes. 3. Interscapular brown adipose tissue (IBAT) mass, adipocyte size, and adipocyte number were greater in obese than in lean. Resting metabolic rates (RMR) of obese rats were lower than in lean, and increased 79% in lean but only 33% in obese animals following NE (200 micrograms/kg BW, s.c.) stimulation. 4. The glycemic response to NE occurred normally in both phenotypes, and resulted in a 3-fold increment in plasma glucose in lean rats and a 5-6-fold increase in plasma glucose in obese rats. 5. The results of this study are consistent with hyperplasia and hypertrophy of IBAT, RP and DOR depots, and indicate that the capacity for non-shivering thermogenesis is impaired in the obese phenotype of this strain in spite of peripheral sensitivity to NE and greater mass and cellularity of brown adipose tissue.     

Fructose transport and metabolism in adipose tissue of Zucker rats: Diminished GLUT5 activity during obesity and insulin resistance

Fructose is a major dietary sugar, which is elevated in the serum of diabetic humans, and is associated with metabolic syndromes important in the pathogenesis of diabetic complications. The facilitative fructose transporter, GLUT5, is expressed in insulin-sensitive tissues (skeletal muscle and adipocytes) of humans and rodents, where it mediates the uptake of substantial quantities of dietary fructose, but little is known about its regulation. We found that GLUT5 abundance and activity were compromised severely during obesity and insulin resistance in Zucker rat adipocytes. Adipocytes from young obese (fa/fa), highly insulin-responsive Zucker rats contained considerably more plasma membrane GLUT5 than those from their lean counterparts (1.8-fold per microgram membrane protein), and consequently exhibited higher fructose transport (fivefold) and metabolism (threefold) rates. Lactate production was the preferred route for fructose metabolism in these cells. As the rats aged and become more obese and insulin-resistant, adipocyte GLUT5 surface density (12-fold) and fructose transport (10-fold) and utilisation rates (threefold) fell markedly. The GLUT5 loss was more dramatic in adipocytes from obese animals, which developed a more marked insulin resistance than lean counterparts. The decline of GLUT5 levels in adipocytes from older, obese animals was not a generalised effect, and was not observed in kidney, nor was this expression pattern shared by the 1 subunit of the Na⁺/K⁺ ATPase. Our findings suggest that plasma membrane GLUT5 levels and thus fructose utilisation rates in adipocytes are dependent upon cellular insulin sensitivity, inferring a possible role for GLUT5 in the elevated circulating fructose observed during diabetes, and associated pathological complications. (Mol Cell Biochem 261: 23–33, 2004)