Circulating leptin levels in newborn rats: a significant post- natal developmental effect,independent of dietary polyunsaturated fat levels

Leptin expression exhibits developmental and dietary regulation, but it is unknown whether there is an interaction of the regulation by dietary fat and postnatal development. The purpose of this study was to test the effect of different levels of dietary polyunsaturated fat on circulating leptin levels at different post-natal developmental stages. Pregnant (Sprague-Dawley) rats consumed from day 15 of pregnancy through day 9 of lactation a low fat, (11% of energy; LF) polyunsaturated safflower oil diet. From day 9 of lactation, dams and their respective pups were fed low, moderate (40% of energy; MF) or high (67% of energy; HF) polyunsaturated safflower oil diets to full maturation (56 days). Diets were iso-energetic and iso-nitrogenous. Milk fatty acid content reflected the mothers and pups diet, with 15 to 100 fold less C10:0 and 2.6 to 3.3 fold more C18:2 in MF and HF groups compared to LF diet. In newborn rats through post-natal day 56, levels of polyunsaturated fat in mothers' milk and mothers/pups diet had no effect on the levels of circulating leptin. The post-natal development period significantly affected circulating leptin levels (p < 0.001, 15 days = 56 days > 21 days > 28 days). In summary, the developmental postnatal stage regulates leptin levels, independently of the polyunsaturated fat levels in the diet.     

Evidence that triiodothyronine decreases rat serum leptin concentration by down-regulation of leptin gene expression in white adipose tissue

Conflicting results have been reported regarding the effect of triiodothyronine (T(3)) on serum leptin and adipose tissue leptin gene expression in human and animals. The aim of the present study was to evaluate the effect of administration of increasing doses of T(3) on serum leptin concentration and on leptin mRNA abundance in white adipose tissue of rats. The results presented in this paper indicate that administration of single different doses of T(3) to euthyroid rats resulted dose dependent increases of serum total T(3) concentrations which are associated with a decrease in white adipose tissue leptin mRNA level. The leptin mRNA level in white adipose tissue was negatively correlated with serum total T(3) concentration (r=-0.8, p<0.001). Like white adipose tissue leptin mRNA level, serum leptin concentration decreased after T(3) administration, and was also negatively correlated with the serum T(3) concentration (r=-0.8, p<0.001). In contrast, administration of T(3) to the same rats led to a significant increase in white adipose tissue expression of the malic enzyme gene (malic enzyme activity and malic enzyme mRNA level), a known target gene for T(3). The results indicate that T(3) exerts a selective inhibitory effect on white adipose tissue leptin gene expression in vivo. A conclusion is that T(3) decreases rat serum leptin concentration by down-regulation of leptin gene expression in white adipose tissue.     

Estrogen improved metabolic syndrome through down-regulation of VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats

Metabolic syndrome (MBS), a cluster of metabolic abnormalities and visceral fat accumulation, increases cardiovascular risks in postmenopausal women. In addition to visceral fat, perivascular adipose tissue has been recently found to play an important role in vascular pathophysiology. Hence, the present study investigates the effects of estrogen on both intra-abdominal fat (visceral fat) and periaortic fat (perivascular fat) accumulation as well as hypoxia in ovariectomized female rats. Female rats were divided into sham operation, ovariectomy and ovariectomy with 17β-estradiol supplementation groups. Twelve weeks later, we found that estrogen improved MBS via reducing body weight gain, the weight of periaortic and intra-abdominal fat, hepatic triglyceride, and total serum cholesterol levels. Estrogen also increased insulin sensitivity through restoring glucose and serum leptin levels. For periaortic fat, western blot showed estrogen inhibited hypoxia by reducing the levels of VEGF and HIF-1α, which is consistent with the results from immunohistochemical staining. The correlation analysis indicated that perivascular fat had a positive correlation with body weight, intra-abdominal fat or serum total cholesterol, but a negative correlation with insulin sensitivity index. For intra-abdominal fat, real-time fluorescent RT-PCR showed estrogen improved fat dysfunction via reducing the levels of relative leptin, MCP-1 but increasing adiponectin mRNA. Estrogen reduced the levels of VEGF and HIF-1α to inhibit hypoxia but restored the levels of PPARγ and Srebp-1c, which are important for lipid capacity function of intra-abdominal fat. These results demonstrated estrogen improved MBS through down-regulating VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats.     

Effects of dietary fat and zinc on adiposity,serum leptin and adipose fatty acid composition in C57BL/6J mice

Zinc (Zn) has been implicated in altered adipose metabolism, insulin resistance and obesity. The objective of this study was to investigate the effects dietary Zn deficiency and supplementation on adiposity, serum leptin and fatty acid composition of adipose triglycerides and phospholipid in C57BL/6J mice fed low-fat (LF) or high-fat (HF) diets for a 16 week period. Weanling C57BL/6J mice were fed LF (16% kcal from soybean oil) or HF (39% kcal from lard and 16% kcal from soybean oil) diets containing 3, 30 or 150 mg Zn/kg diet (ZD = Zn-deficient, ZC = Zn control and ZS = Zn-supplemented, respectively). HF-fed mice had higher fat pad weights and lower adipose Zn concentrations than the LF-fed mice. The ZD and ZS groups had a reduced content of fatty acids in adipose triglycerides compared to the ZC group, suggesting that zinc status may influence fatty acid accumulation in adipose tissue. Serum leptin concentration was positively correlated with body weight and body fat, and negatively correlated with adipose Zn concentration. Dietary fat, but not dietary Zn, altered the fatty acid composition of adipose tissue phospholipid and triglyceride despite differences in Zn status assessed by femur Zn concentrations. The fatty acid profile of adipose triglycerides generally reflected the diets. HF-fed mice had a higher percentage of C20:4 n-6, elevated ratio of n-6/n-3, lower ratio of PUFA/SAT and reduced percentage of total n-3 fatty acids in adipose phospholipid, a fatty acid profile associated with obesity-induced risks for insulin resistance and impaired glucose transport. In summary, the reduced adipose Zn concentrations in HF-fed mice and the negative correlation between serum leptin and adipose Zn concentrations support an interrelationship among obesity, leptin and Zn metabolism.     

Effects of dietary fat type and energy restriction on adipose tissue fatty acid composition and leptin production in rats

To investigate whether dietary fatty acid (FA) composition and energy restriction (ER) interactively influence obese (ob) gene expression, rats consumed diets containing beef tallow, safflower, or fish oil ad libitum (AL) or at 60% AL intake. Circulating leptin concentrations were higher (P < 0.0001) after AL feeding, but were not influenced by dietary fat. ER decreased (P < 0.0001) weight gain and visceral adipose weight, which were positively correlated (r = 0.40 P < 0.001, r = 0.58 P < 0.0001) with circulating leptin levels. Visceral adipose ob mRNA levels were greater in animals fed unsaturated fats, particularly safflower oil, which had the highest ob mRNA levels. Circulating leptin levels did not parallel ob mRNA levels, except for the greater abundance detected in AL adipose in comparison to ER animals. In addition, visceral FA profiles reflected dietary fat source and were influenced by an interaction of dietary fat and energy. These data demonstrate that dietary fat, particularly from a plant or marine source, and ER interactively influence ob mRNA levels; however, alterations in ob mRNA do not confer changes in circulating leptin, with the exception of ER, which is a key determinant. Thus, dietary intake is an important regulator of leptin production; however, the significance of these modest changes in diet-induced obese animals requires further study.     

Muscle adaptations to hindlimb suspension in mature and old Fischer 344rats

Stump, Craig S., Charles M. Tipton, and Erik J. Henriksen.Muscle adaptations to hindlimb suspension in mature and oldFischer 344 rats. J. Appl. Physiol.82(6): 1875-1881, 1997.We examined skeletal and cardiac muscleresponses of mature (8 mo) and old (23 mo) male Fischer 344 rats to 14 days of hindlimb suspension. Hexokinase (HK) and citrate synthase (CS)activities and GLUT-4 glucose transporter protein level, which arecoregulated in many instances of altered neuromuscular activity, wereanalyzed in soleus (Sol), plantaris (Pl), tibialis anterior (TA),extensor digitorum longus (EDL), and left ventricle. Protein contentwas significantly (P < 0.05) lowerin all four hindlimb muscles after suspension compared with controls inboth mature (21-44%) and old (17-43%) rats. Old ratsexhibited significantly lower CS activities than mature rats for theSol, Pl, and TA. HK activities were significantly lower in the old ratsfor the Pl (19%) and TA (33%), and GLUT-4 levels were lower in theold rats for the TA (38%) and EDL (24%) compared with the maturerats. Old age was also associated with a decrease in CS activity (12%)and an increase in HK activity (14%) in cardiac muscle. CS activitieswere lower in the Sol (20%) and EDL (18%) muscles from maturesuspended rats and in the Sol (25%), Pl (27%), and EDL (25%) musclesfrom old suspended rats compared with corresponding controls. However,suspension was associated with significantly higher HK activities forall four hindlimb muscles examined, in both old (16-57%) andmature (10-43%) rats, and higher GLUT-4 concentrations in the TAmuscles of the old rats (68%) but not the mature rats. These resultsindicate that old age is associated with decreased CS and HK activities and GLUT-4 protein concentration for several rat hindlimb muscles, andthese variables are not coregulated during suspension. Finally, old ratskeletal muscle appears to respond to suspension to a similar orgreater degree than mature rat muscle responds.

     

Effect of orchidectomy and testosterone substitution on enzyme activities and DNA content in rat liver and epididymal fat

Orchidectomy of rats resulted in increased concentration and whole organ amount of DNA both in the epididymal fat pad and liver. Liver hexokinase (HK) and phosphofructokinase (PFK) activities were raised after orchidectomy, but were normalized by testosterone substitution. Several glycolytic enzymes, and fumarase and aspartate aminotransferase were increased by orchidectomy in epididymal fat. Most of the enzyme changes tended to normalize after testosterone administration. Activities of NADPH generating enzymes were increased after orchidectomy both in liver and epididymal fat. When related to DNA, several enzyme activities in both tissues fell following castration. However, liver HK, PFK and NADPH generating enzymes, as well as epididymal fat HK and isocitrate dehydrogenase were elevated after castration also when related to DNA. The results suggest that the influence of testosterone on cell proliferation is organ-specific. The observed enzyme alterations after orchidectomy might partly explain fat accumulation and hyperlipoproteinemia encountered in castrates.     

Effect of ovarian hormones on mitochondrial enzyme activity in the fat oxidation pathway of skeletal muscle

To examine the roles of 17beta-estradiol (E(2)) and progesterone (Prog) in lipid metabolism, skeletal muscle enzyme activities were studied in female Sprague-Dawley rats. Groups included sham-operated rats (C) and ovariectomized rats treated with placebo (O), E(2) (E), Prog (P), both hormones at physiological doses (P + E), or both hormones with a high dose of E(2) (P + HiE). Hormone (or vehicle only) delivery was via time-release pellets inserted at the time of surgery, 15 days before metabolic testing. Results demonstrated that carnitine palmitoyltransferase maximal activity was 19, 21, and 19% lower (P < 0.01) in O, P, and P + E rats, respectively, compared with C rats. Conversely, activity in E and P + HiE rats was 14 and 19% higher (P < 0.01) than in C. beta-Hydroxyacyl-CoA dehydrogenase (beta-HAD) maximal activity was 20% lower (P < 0.01) in O than in C rats; similarly, P and P + E rats were 18 and 19% lower, respectively (P < 0.01); however, treatment with E(2) returned beta-HAD activity to C levels. These results suggest that E(2) plays a role in lipid metabolism by increasing the maximal activity of key enzymes in the fat oxidative pathway of skeletal muscle.     

Subcutaneous lipectomy causes a metabolic syndrome in hamsters

The insulin resistance syndrome X is related to excess intra-abdominal adipose tissue. With lipectomy of >50% of subcutaneous adipose tissue (SQAT) in nonhibernating, adult female Syrian hamsters on high-fat (HF; 50 calorie%) diet and measurements of oral glucose tolerance, oral [(14)C]oleic acid disposal, serum triglycerides, serum leptin, liver fat, perirenal (PR) adipose tissue cellularity, and body composition, we studied the role of SQAT. Sham-operated (S) animals on HF or low-fat (LF; 12.5 calorie%) diets served as controls. After 3 mo there was no visible regrowth of SQAT but HF diet led to similar levels of body weight and body fat in lipectomized and sham-operated animals. Lipectomized (L) animals had more intra-abdominal fat as a percentage of total body fat, higher insulinemic index, a strong trend toward increased liver fat content, and markedly elevated serum triglycerides compared with S-HF and S-LF. Liver and PR adipose tissue uptake of fatty acid were similar in L-HF and S-HF but reduced vs. S-LF, and were inversely correlated with liver fat content and insulin sums during the oral glucose tolerance test. In summary, lipectomy of SQAT led to compensatory fat accumulation implying regulation of total body fat mass. In conjunction with HF diet these lipectomized hamsters developed a metabolic syndrome with significant hypertriglyceridemia, relative increase in intra-abdominal fat, and insulin resistance. We propose that SQAT, via disposal and storage of excess ingested energy, acts as a metabolic sink and protects against the metabolic syndrome of obesity.     

Age-associated changes in fat metabolism in the rat and its relation to sympathetic activity

In this study, to determine if age associated changes in fat metabolism in skeletal muscle and liver were related with sympathetic activity, we measured sympathetic activity and palmitate oxidation rate, carnitine palmitoyltransferase-1 (CPT-1) activity, and triglyceride concentration in skeletal muscle and liver of rats at 8, 30 and 60 weeks of age. Body weight, intra-abdominal percent of fat mass, and plasma level of insulin, leptin, and triglyceride were all significantly increased with age. Tissue triglyceride concentration was increased with age in liver and skeletal muscle. The palmitate oxidation rate in liver and skeletal muscle was reduced with age in rats and inversely correlated with tissue triglyceride concentration. CPT-1 activity was not altered with age. Plasma catecholamine concentration and sympathetic activity, as measured by spectral analysis of heart rate variability, were increased with age. Plasma norepinephrine or epinephrine and tissue triglyceride had a positive correlation in liver and skeletal muscle. Plasma norepinephrine or epinephrine to tissue triglyceride ratio was similar according to age. In summary, in spite of increased sympathetic activity with age, the tissue triglyceride concentration was increased. Increased sympathetic activity may be the compensatory response and the reduced capacity of fatty acid oxidation is a main cause of obesity.     

Aging and respiratory muscle metabolic plasticity: effects of endurance training.

We examined the oxidative and antioxidant enzyme activities in respiratory and locomotor muscles in response to endurance training in young and aging rats. Young adult (4-mo-old) and old (24-mo-old) female Fischer 344 rats were divided into four groups: 1) young trained (n = 12), 2) young untrained (n = 12), 3) old trained (n = 10), and 4) old untrained (n = 6). Both young and old endurance-trained animals performed the same training protocol during 10 wk of continuous treadmill exercise (60 min/day, 5 days/wk). Compared with young untrained animals, the young trained group had significantly elevated (P less than 0.05) activities of 3-hydroxyacyl-CoA dehydrogenase (HADH), glutathione peroxidase (GPX), and citrate synthase (CS) in both the costal diaphragm and the plantaris muscle. In contrast, training had no influence (P greater than 0.05) on the activity of lactate dehydrogenase within the costal diaphragm in young animals. In the aging animals, training did not alter (P greater than 0.05) activities of CS, HADH, GPX, or lactate dehydrogenase in the costal diaphragm but significantly (P less than 0.05) increased CS, HADH, and GPX activities in the plantaris muscle. Furthermore, training resulted in higher activities of CS and HADH in the intercostal muscles in the old trained than in the old untrained animals. Finally, activities of CS, HADH, and GPX were significantly (P less than 0.05) lower in the plantaris in the old untrained than in the young untrained animals; however, CS, HADH, and GPX activities were greater (P less than 0.05) in the costal diaphragm in the old sedentary than in the young untrained animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of overfeeding on myofibre characteristics and metabolical traits of the breast muscle in Muscovy ducks (Caïrina moschata)

The aim of this experiment was to study the consequences of precise feeding on the myofibre characteristics and metabolic traits of the breast muscle (Pectoralis major, Pm) of Muscovy ducks. Twenty-four samples of breast muscle, without skin or subcutaneous fat, from two groups of ducks, control and overfed respectively, were collected at 14 weeks of age. We assayed different chemical (water content, crude proteins, total lipid ashes, total and thermosoluble collagen), biochemical (activities of the CS, LDH and beta-HAD enzymes), histological (muscle fibre typing and intramuscular adipocyte measurements) and technological (drip and cooking losses, texture) determinations. At the force-feeding period, the overfed ducks weighed 6366 g and the control ducks 4606 g of body weight. In the PM muscle, some modifications of the biochemichal parameters and enzyme activities were observed but neither the shear force nor the histological characteristics of the breast muscle were affected by the fattening treatment. The overfed birds had an increased total lipids content (correlated to an increase in the intramuscular area occupied by the adipocyte) and a different fatty acid profile as the result of a higher energy feed intake. The lipids of the Pm muscle of the overfed ducks contained more C16:0, C16:1n-7 and C18:1n-9, but less C18:0, C18:2n-6 and C20:4n-6 than the control birds. These results show that in response to high energy feeding, the muscle is able to respond quickly on a metabolic basis (by increasing the activities of the oxydative enzymes) without changing its typology or morphology. Additionally, fattening was correlated to a degradation in the technological qualities of the breast muscle, especially an increase in the cooking losses.     

Effect of exercise training on in vivo lipolysis in intra-abdominal adipose tissue in rats

Intra-abdominal obesity is associated with cardiovascular disease and non-insulin-dependent diabetes mellitus, and physical training has been suggested to alleviate these conditions. We compared epinephrine-stimulated lipolysis in vivo in three intra-abdominal adipose tissues (ATs: retroperitoneal, parametrial, and mesenteric) and in subcutaneous AT, and we also studied the effect of physical training. Moreover, we studied the effect of physical training on epinephrine-stimulated lipolysis in muscle in vivo. Female rats were either swim trained (15 wk, n = 8) or sedentary (n = 7). Under anesthesia, a two-stage intravenous epinephrine infusion (60 min of 80 and 200 ng. kg(-1). min(-1), respectively) was carried out, and local interstitial glycerol concentration was measured by the microdialysis technique. Blood flow was measured by microspheres. Training increased blood flow in all ATs [on average: 73 +/- 12 (trained) vs. 14 +/- 4 (sedentary) ml. 100 g(-1). min(-1), P < 0. 05]; nevertheless, epinephrine-stimulated interstitial glycerol concentrations were increased or unchanged. Interstitial glycerol concentration was higher in intra-abdominal than in subcutaneous AT in both trained and sedentary rats. In skeletal muscle, interstitial glycerol concentration and blood flow did not differ between trained and sedentary rats. In conclusion, in vivo lipolysis is higher both in the basal state and during epinephrine-stimulation in intra-abdominal than in subcutaneous AT, and training may be beneficial in alleviating intra-abdominal obesity by enhancing lipolysis in intra-abdominal fat depots.     

Recovered insulin response by 2 weeks of leptin administration in high-fat fed rats is associated with restored AS160 activation and decreased reactive lipid accumulation

Leptin is an adipokine that increases fatty acid (FA) oxidation, decreases intramuscular lipid stores, and improves insulin response in skeletal muscle. In an attempt to elucidate the underlying mechanisms by which these metabolic changes occur, we administered leptin (Lep) or saline (Sal) by miniosmotic pumps to rats during the final 2 wk of a 6-wk low-fat (LF) or high-fat (HF) diet. Insulin-stimulated glucose transport was impaired by the HF diet (HF-Sal) but was restored with leptin administration (HF-Lep). This improvement was associated with restored phosphorylation of Akt and AS160 and decreased in reactive lipid species (ceramide, diacylglycerol), known inhibitors of the insulin-signaling cascade. Total muscle citrate synthase (CS) activity was increased by both leptin and HF diet, but was not additive. Leptin increased subsarcolemmal (SS) and intramyofibrillar (IMF) mitochondria CS activity. Total muscle, sarcolemmal, and mitochondrial (SS and IMF) FA transporter (FAT/CD36) protein content was significantly increased with the HF diet, but not altered by leptin. Therefore, the decrease in reactive lipid stores and subsequent improvement in insulin response, secondary to leptin administration in rats fed a HF diet was not due to a decrease in FA transport protein content or altered cellular distribution.     

Serum leptin, lipids, free fatty acids, and fat pads in long-term dehydroepiandrosterone-treated Zucker rats

The obese Zucker rat has a genetically flawed leptin system and is a model of hyperphagia, obesity, hyperlipidemia, and markedly elevated leptin levels. Dehydroepiandrosterone (DHEA) administration reduces hyperphagia, hyperlipidemia, and obesity in Zucker rats. Since serum leptin levels are associated with body fat, we wondered what the effects of fat pad weight reduction from DHEA administration would have on leptin levels. This experiment investigated the effects of DHEA on intra-abdominal fat pads, serum lipids, and peripheral leptin in male lean and obese Zucker rats that were administered DHEA in their food from 4 weeks of age to 20 weeks. Lean and obese rats received plain chow or chow containing DHEA. Additional chow-fed groups of lean and obese weight-matched controls and obese pair-fed rats helped to control for the reduced body weight, food intake, and fat pad weights seen with DHEA administration. DHEA administration to lean Zucker rats reduced body weight and fat pad weights, but leptin levels showed a lower trend. Among obese rats, both DHEA treatment and pair-feeding reduced body weight and fat pad weights, but only DHEA lowered leptin levels. The weight-matched controls had reductions in fat pad weights similar to the DHEA-treated group, but with increased leptin levels. Thus, DHEA may exert a small, independent effect on leptin levels in this animal model, but the reduction is less than what would be expected.     

Comparative cryopreservation of avian spermatozoa: effects of freezing and thawing rates on turkey and sandhill crane sperm cryosurvival

In beef cows, reduced energy intake delays first ovulation postpartum and is associated with lesser insulin, IGF-I and leptin concentrations. However, the close relationship among these hormones mask their individual roles in the reinitiation of ovarian activity. A β-adrenergic receptor agonist (βAR) was used to increase body condition score (BCS) and yet reduce body fat and leptin serum concentration to determine the specific role of leptin in the postpartum ovarian activity. Beef cows (n=77) with BCS 3.1 ± 1.4 received 2 kg/day of feed containing 0 or 0.15 mg/kg of zilpaterol (a synthethic βAR), for 33 days. Estrus was induced with a progestin implant applied for 9 d and cows in estrus were bred by artificial insemination (AI). Zilpaterol administration increased (P<0.05) daily weight gain, muscle depth and BCS, with no changes in back fat depth, reducing fat to muscle ratio (P<0.05). At the time of AI, insulin (38%) and IGF-I (26%) concentrations were less in zilpaterol-treated cows (P<0.05), but leptin concentration was unaffected. Ovulation rate and animal with luteal activity after estrus induction were also reduced by 35% (P=0.05) and 56.5% (P=0.007), respectively, in zilpaterol-treated cows. Logistic regression estimates for BCS (P=0.016) and IGF-I concentration (P=0.03) were positively related with the occurrence of luteal activity. In addition, whilst back fat (P=0.009) had a positive effect on luteal activity, leptin concentration did not show a significant relationship. In conclusion, despite an increase in body weight and a positive change in BCS, the reduction in insulin and IGF-I concentrations, associated with βAR treatment, reduced the response to induction of estrus. However only IGF-I, but not leptin or insulin, significantly influenced the odds for the occurrence of luteal activity after estrous induction in cattle with poor BCS.     

Serum leptin concentration in pigs selected for high or low daily food intake

Selection for high or low daily food intake (DFI) in Large White pigs resulted in higher serum leptin concentration, fat deposition and food intake in the high DFI line. The response in serum leptin concentration indicated that the higher fat deposition of the high DFI line was not due to insufficient leptin production, as in the Lepob/Lepob mouse. Serum leptin was more highly correlated with fat deposition than with food intake indicating that the response in serum leptin was primarily due to increased fat deposition rather than to higher energy intake per se. The low correlations between serum leptin measured at 30 kg and performance test traits indicate that serum leptin would not be efficient for selection of animals prior to performance test. However, the consistent positive correlations between serum leptin and a measure of fat deposition suggest that serum leptin could usefully be incorporated in selection criteria for genetic improvement of carcass lean content in pigs.     

Long-term effects of malnutrition during lactation on the thyroid function of offspring.

Some studies have shown that the mother's nutritional condition may influence offspring's endocrine function through metabolic imprinting. Recently, we showed that the kind of maternal malnutrition during lactation affects adult body weight of the offspring and it is related to milk composition. We studied lactating rats fed an 8 % protein-restricted diet (PR), a control 23 % protein diet (C), and an energy-restricted diet group (ER). After weaning, all animals received a normal diet until they were 180 days of age. At this time, the animals received a single i. p. injection of (131)I and were sacrificed 2 h after the injection. Total triiodothyronine (TT3) and total thyroxin (TT4) serum concentrations were measured by enzyme immunoassay. The PR group had significantly a higher thyroid (131)I uptake, TT3 serum concentration and in TT4 serum concentration, compared to the controls. The ER group had only significantly higher TT3 serum concentration. These results showed that thyroid function regulation in adulthood may depend on maternal nutritional condition during lactation. Probably, PR group had a high thyroid function, whereas the ER group only had an increase in the deiodination of T4. The hyperthyroidism in the PR group could explain the low body weight observed in those animals.     

Overeating of palatable food is associated with blunted leptin and ghrelin responses

Palatable food is rich in fat and/or sucrose. In this study we examined the long-term effects of such diets on food intake, body weight, adiposity and circulating levels of the satiety peptide leptin and the hunger peptide ghrelin. The experiments involved rats and mice and lasted 5 weeks. In rats, we examined the effect of diets rich in fat and/or sucrose and in mice the effect of a high fat diet with or without sucrose in the drinking water. Animals fed with the palatable diets had a larger intake of calories, gained more weight and became more adipose than animals fed standard rat chow. Fasted animals are known to have low serum leptin and high serum ghrelin and to display elevated serum leptin and lowered serum ghrelin postprandially. With time, a sucrose-rich diet was found to raise the fasting level of leptin and to lower the fasting level of ghrelin in rats. A fat-rich diet suppressed serum ghrelin without affecting serum leptin; high sucrose and high fat in combination greatly reduced serum ghrelin and raised serum leptin in the fasted state. The mRNA expression of leptin in the rat stomach was up-regulated by sucrose-rich (but not by fat-rich) diets, whereas the expression of ghrelin seemed not to be affected by the palatable diets. Mice responded to sucrose in the drinking water with elevated serum leptin (fasted state) and to all palatable diets with low serum ghrelin. The expression of both leptin and ghrelin mRNA in the stomach was suppressed in fasted mice that had received a high fat diet for 5 weeks. We conclude that the expression of leptin mRNA in stomach and the concentration of leptin in serum were elevated in response to sucrose-rich rather than fat-rich diets, linking leptin with sucrose metabolism. In contrast, the expression of ghrelin and the serum ghrelin concentration were suppressed by all palatable diets, sucrose and fat alike. In view of the increased body weight and adiposity neither elevated leptin nor suppressed ghrelin were able to control/restrain the overeating that is associated with palatable diets.