Adipose Tissue Leptin mRNA Research Articles

Elafin inhibits obesity, hyperglycemia, and liver steatosis in high-fat diet-treated male mice

Elafin is an antimicrobial and anti-inflammatory protein. We hypothesize that elafin expression correlates with diabetes. Among non-diabetic and prediabetic groups, men have significantly higher serum elafin levels than women. Men with type 2 diabetes mellitus (T2DM) have significantly lower serum elafin levels than men without T2DM. Serum elafin levels are inversely correlated with fasting blood glucose and hemoglobin A1c levels in men with T2DM, but not women with T2DM. Lentiviral elafin overexpression inhibited obesity, hyperglycemia, and liver steatosis in high-fat diet (HFD)-treated male mice. Elafin-overexpressing HFD-treated male mice had increased serum leptin levels, and serum exosomal miR181b-5p and miR219-5p expression. Transplantation of splenocytes and serum exosomes from elafin-overexpressing HFD-treated donor mice reduced food consumption and fat mass, and increased adipose tissue leptin mRNA expression in HFD-treated recipient mice. Elafin improved leptin sensitivity via reduced interferon-gamma expression and induced adipose leptin expression via increased miR181b-5p and miR219-5p expression. Subcutaneous and oral administration of modified elafin inhibited obesity, hyperglycemia, and liver steatosis in the HFD-treated mice. Circulating elafin levels are associated with hyperglycemia in men with T2DM. Elafin, via immune-derived miRNAs and cytokine, activates leptin sensitivity and expression that subsequently inhibit food consumption, obesity, hyperglycemia, and liver steatosis in HFD-treated male mice.

The effect of obesity, impaired carbohydrate metabolism and bariatric surgery on adiponectin and leptin mRNA levels in different adipose tissue depots

Objective. To determine the effect of morbid obesity, impaired carbohydrate metabolism and bariatric surgery on adiponectin and leptin mRNA levels in subcutaneous and visceral adipose tissue.Design and methods. The study included 30 obese female patients. Eleven patients had co-existent impaired carbohydrate metabolism. The control group consisted of 10 healthy non-obese women. In all obese patients, subcutaneous and visceral adipose tissue samples were taken during bariatric surgery. In obese patients 1 year after the intervention and in control individuals subcutaneous adipose tissue samples were collected. The circulating levels of adiponectin and leptin were determined by the enzyme immunoassay. The amount of adiponectin and leptin mRNA in adipose tissue were analyzed by real-time polymerase chain reaction.Results.During the first postoperative year, all patients showed a monotonous decrease in body mass index. After the surgery, the circulating levels of adiponectin and leptin returned to reference values (for healthy population). Compared with the control group, obese patients showed 1,4-times lower adiponectin mRNA level (p < 0,01) in subcutaneous adipose tissue, while leptin mRNA level did not change. In obese patients with impaired carbohydrate metabolism, the adiponectin mRNA level was twice lower in visceral adipose tissue (p < 0,01), compared to patients without impaired carbohydrate metabolism. In obese patients with and without impaired carbohydrate metabolism, mRNA levels of adipokines were more than 2-times lower in visceral adipose tissue compared to subcutaneous adipose tissue (p < 0,05). In subcutaneous adipose tissue, 1 year after bariatric intervention, adiponectin mRNA level decreases by 4,5 times (p < 0,01) in obese patients, and leptin mRNA level decreases by 3,1 times (p < 0,01) in patients with obesity and by 1,5 times (p < 0,05) in patients with obesity and impaired carbohydrate metabolism. Neither adiponectin nor leptin mRNA levels from adipose tissue of different localization showed statistically significant correlation. No correlation was found between the levels of circulating adipokines and their mRNA amount in adipose tissue.Conclusions.Our results indicate that adiponectin and leptin mRNA levels in adipose tissue cells depend on their localization in the body, as well as the presence of obesity and impaired carbohydrate metabolism. We also showed that adiponectin and leptin mRNA levels in adipose tissue change in response to bariatric surgery.

The expression of leptin, hypothalamic neuropeptides and UCP1 before, during and after fattening in the Daurian ground squirrel (Spermophilus dauricus)

The Daurian ground squirrel (Spermophilus dauricus) accumulates large amounts of body fat during pre-hibernation fattening. Leptin, an adipose-derived hormone, plays important roles in energy balance and thermogenesis. We predicted that body fat accumulation would lead to the elevation of leptin concentration while its effect on satiety would be suppressed in hypothalamus during fattening. In addition, the uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) would increase and correlated positively with leptin concentration before hibernation. Here, we measured serum leptin concentration and leptin mRNA in white adipose tissue (WAT), hypothalamic neuropeptides involved in energy regulation and UCP1 in BAT before, during and after fattening in squirrels. The fat mass gradually increased during fattening but serum leptin increased mainly in the late phase of fattening, which was consistent with leptin mRNA expression in WAT. During fattening, the mRNA of hypothalamic leptin receptor was up-regulated and correlated positively with serum leptin. Orexigenic neuropeptide Y mRNA increased by 67%; however agouti-related peptide remained unchanged before hibernation. There was no significant change in anorexigenic neuropeptide mRNA. No change in suppressor of cytokine signaling-3 and protein tyrosine phosphatase-1B was detected. UCP1 mRNA expression and protein content in BAT increased significantly after fattening. These changes were independent of environmental conditions and serum leptin concentration. Our results suggest that the dissociation of leptin production and adiposity during fattening may facilitate fat accumulation. No evidence of suppressed leptin signal was found in fattening squirrels. The UCP1 recruitment in post-fattening squirrels could occur without winter-like acclimation and increased leptin.

Fetal life malnutrition is not reflected in the relative abundance of adiponectin and leptin mRNA in adipose tissue in male mink kits at 9.5 weeks of age

Malnutrition in fetal life and during suckling have in some animal studies resulted in adaptive changes related to the fat and glucose metabolism, which in the long term might predispose the offspring for metabolic disorders such as obesity later in life. The objective was to study the effect of fetal life malnutrition in male mink on the gene expression of leptin and adiponectin in different adipose tissue sites. Thirty-two male mink, strict carnivore species, exposed to low (FL) or adequate (FA) protein provision the last 16.3 ± 1.8 days of fetal life and randomly assigned to a low (LP) or adequate (AP) protein diet from 7 to 9.5 weeks of age were used. Adipose tissues (subcutaneous, perirenal and mesenteric) were analyzed using qPCR. Fetal life or post-weaning protein provision did not affect the relative abundances of leptin and adiponectin mRNAs in adipose tissue at 9.5 weeks of age. Relative abundances of leptin and adiponectin mRNAs were different between adipose tissue sites and were significantly higher in subcutaneous than in perirenal and mesenteric tissues. Fetal life protein malnutrition in male mink, did not result in adaptive changes in the gene expression of leptin and adiponectin mRNAs in adipose tissue at 9.5 weeks of age as found in rodents. However, both leptin and adiponectin mRNAs were significantly differently expressed between tissue sites.

Maternal prolactin inhibition causes changes in leptin at 22- and 30-day-old pups.

Breastfeeding is associated with obesity prevention. We showed previously that prolactin inhibition at the end of lactation causes hyperleptinemia at weaning (PN21) and programs for obesity, insulin resistance, dyslipidemia, and leptin resistance (PN180). Here, we evaluate the source of neonatal hyperleptinemia and how it develops during the nutritional transition from milk through solid food. Lactating rats were treated with bromocriptine (BRO), a prolactin inhibitor, 0.5 mg twice a day, or saline (CON) for the last 3 days of lactation. All parameters were studied at PN22 and PN30. At PN22, BRO-treated rats showed lower food intake, body mass, and body length. At PN30, only body length and mesenteric fat mass were lower. Despite normal plasma leptin levels at PN22, the adipose tissue leptin mRNA expression was lower, while plasma leptin was higher in PN30, possibly due to a higher adipose mesenteric tissue production. At PN22, the hypothalamus seems to be more sensitive to leptin, since OBR and STAT3 are higher. Conversely, at PN30 leptin signaling pathway is suggestive of leptin resistance with lower STAT3 and higher SOCS3 in hypothalamus and consequently higher NPY. Glycemia was lower at PN22 and higher at PN30, without changes in plasma insulin levels. At PN30, BRO-treated rats had other metabolic changes such as higher plasma cholesterol, lower HDL-c, higher hepatic cholesterol and AST, suggesting a liver dysfunction. Our data show that milk supply can exert a crucial role in the imprinting of a second leptin peak, which is important for survival adaptation to adverse nutritional conditions.

Endothelial cell leptin receptor mutant mice have hyperleptinemia and reduced tissue uptake

Hyperleptinemia is usually associated with obesity and leptin resistance. Endothelial cell leptin receptor knockout (ELKO) mice without a signaling membrane-bound leptin receptor in endothelia, however, have profound hyperleptinemia without signs of leptin resistance. Leptin mRNA in adipose tissue was unchanged. To test the hypothesis that the ELKO mutation results in delayed degradation and slowed excretion, we determined the kinetics of leptin transfer in groups of ELKO and wildtype mice after intravenous bolus injection of (125) I-leptin and the reference substance (131) I-albumin. The degradation pattern of (125) I-leptin in serum and brain homogenates at different time points between 10 and 60 min was measured by HPLC and acid precipitation. Although ELKO mice had reduced uptake of (125) I-leptin uptake by the brain and several peripheral organs, leptin was more stable in blood and tissue. There was no change in the rate of renal excretion. ELISA showed that serum soluble leptin receptor, known to antagonize leptin transport, had a 400-fold increase, probably contributing to the hyperleptinemia and reduced tissue uptake. Thus, the ELKO mutation unexpectedly increased the stability of leptin but suppressed its tissue uptake. These changes probably contribute to the known partial resistance of the ELKO mice to diet-induced obesity.

The increase of serum chemerin concentration is mainly associated with the increase of body mass index in obese, non-diabetic subjects.

Chemerin is a newly discovered adipokine, whose circulating concentration is increased in obesity. To elucidate whether the increased circulating chemerin concentrations in obese subjects are associated with the increase of fat mass, the increase in chemerin gene expression in adipose tissue or both. Serum chemerin concentrations in 20 non-obese healthy volunteers and 21 non-diabetic obese subjects were measured using ELISA. Chemerin mRNA and chemerin protein levels in visceral and subcutaneous adipose tissues of obese subjects were analyzed by Real-Time PCR and Western blot respectively. We found that the serum chemerin concentrations were significantly higher in obese subjects than in controls and positively correlated with BMI, fat mass and body mass. Moreover serum chemerin concentrations were correlated positively with serum CRP concentrations independently of BMI. No correlation was found between the chemerin mRNA and chemerin protein levels in visceral and subcutaneous adipose tissues and BMI, fat mass, or body weight. Likewise, there was no correlation between the serum chemerin concentrations and the levels of chemerin mRNA and protein in adipose tissue of obese patients. Multiple regression analysis suggests that BMI was the main predictor of serum chemerin concentration. In contrast to chemerin, both serum leptin concentrations and adipose tissue leptin mRNA levels positively correlated with BMI. The results presented here indicate that serum chemerin concentrations correlated with BMI, whereas chemerin mRNA levels in adipose tissue did not. Thus the elevated circulating chemerin concentration in obese, non-diabetic patients was mainly associated with the increased BMI.

Functional changes in adipose tissue in a randomised controlled trial of physical activity.

BackgroundA sedentary lifestyle predisposes to cardiometabolic diseases. Lifestyle changes such as increased physical activity improve a range of cardiometabolic risk factors. The objective of this study was to examine whether functional changes in adipose tissue were related to these improvements.MethodsSeventy-three sedentary, overweight (mean BMI 29.9 ± 3.2 kg/m2) and abdominally obese, but otherwise healthy men and women (67.6 ± 0.5 years) from a randomised controlled trial of physical activity on prescription over a 6-month period were included (control n = 43, intervention n = 30). Detailed examinations were carried out at baseline and at follow-up, including fasting blood samples, a comprehensive questionnaire and subcutaneous adipose tissue biopsies for fatty acid composition analysis (n = 73) and quantification of mRNA expression levels of 13 candidate genes (n = 51), including adiponectin, leptin and inflammatory cytokines.ResultsAt follow-up, the intervention group had a greater increase in exercise time (+137 min/week) and a greater decrease in body fat mass (−1.5 kg) compared to the control subjects (changes of 0 min/week and −0.5 kg respectively). Circulating concentrations of adiponectin were unchanged, but those of leptin decreased significantly more in the intervention group (−1.8 vs −1.1 ng/mL for intervention vs control, P < 0.05). The w6-polyunsaturated fatty acid content, in particular linoleic acid (18:2w6), of adipose tissue increased significantly more in the intervention group, but the magnitude of the change was small (+0.17 vs +0.02 percentage points for intervention vs control, P < 0.05). Surprisingly leptin mRNA levels in adipose tissue increased in the intervention group (+107% intervention vs −20% control, P < 0.05), but changes in expression of the remaining genes did not differ between the groups.ConclusionsAfter a 6-month period of increased physical activity in overweight elderly individuals, circulating leptin concentrations decreased despite increased levels of leptin mRNA in adipose tissue. Otherwise, only minor changes occurred in adipose tissue, although several improvements in metabolic parameters accompanied the modest increase in physical activity.

제 2형 당뇨쥐에서 동충하초로부터 생산된 세포외 다당류의 항당뇨 효과

Anti-diabetic effect of the exopolysaccharides (EPS) produced from submerged mycelial culture of Cordyceps sinensis (Cs) was studiedin a type II diabetic animal model (C57BL/6J ob/ob). This study was designed to determine whether Cs-EPS improves clinical symptoms of type II diabetes in ob/ob mice. After Cs-EPS treatment at doses of 200 mg/kg body weight, the fasting blood glucose levels decreased by 47% after 7 weeks compared with those of the control mice. According to the oral glucose tolerance test, the glucose levels recovered its baseline after 120 min in Cs-EPS-treated mice, although the blood glucose levels increased significantly after 30 min. On the other hand, the control group (not-treated) did not recovered its initial level of glucose after 120 min. Furthermore, food intake, body weight, total plasma cholesterol and triglyceride concentrations in ob/ob mice treated with Cs-EPS were significantly decreased, compared with those in control ob/ob mice. Cs-EPS treatment increased significantly the plasma insulin level and the expression of leptin mRNA in adipose tissue of Cs-EPS-treated ob/ob mice. From these results, it is demonstrated that Cs-EPS could be effective for regulating normal blood glucose levels by increasing the amounts of plasma insulin and leptin expression in ob/ob mice, indicating that this compound could be a candidate material as a dietary supplement to control hyperglycemia in patients suffering from type II diabetes.

Lipoic acid inhibits leptin secretion and Sp1 activity in adipocytes

Lipoic acid (LA) is an antioxidant with therapeutic potential on several diseases such as diabetes and obesity. Hyperleptinemia and oxidative stress play a major role in the development of obesity-linked diseases. The aim of this study was to examine in vivo and in vitro the effects of LA on leptin production, as well as to elucidate the mechanisms and signalling pathways involved in LA actions. Dietary supplementation with LA decreased both circulating leptin, and adipose tissue leptin mRNA in rats. Treatment of 3T3-L1 adipocytes with LA caused a concentration-dependent inhibition of leptin secretion and gene expression. Moreover, LA stimulated the anaerobic utilization of glucose to lactate, which negatively correlated with leptin secretion. Furthermore, LA enhanced phosphorylation of Sp1 and inhibited Sp1 transcriptional activity in 3T3-L1 adipocytes. Moreover, LA inhibited Akt phosphorylation, a downstream target of phosphatidylinositol 3-kinase (PI3K). Treatment with the PI3K inhibitor LY294002 mimicked LA actions, dramatically inhibiting both leptin secretion and gene expression and stimulating Sp1 phosphorylation. All of these data suggest that the phosphorylation of Sp1 and the accompanying reduced DNA-binding activity are likely to be involved in the inhibition of leptin induced by LA, which could be mediated in part by the abrogation of the PI3K/Akt pathway.

Novel porcine housekeeping genes for real-time RT-PCR experiments normalization in adipose tissue: Assessment of leptin mRNA quantity in different pig breeds

The main function of adipose tissue is energy storage and production of various cytokines and hormones, such as leptin. Leptin is a protein hormone synthesized and secreted by adipose tissue. The expression of leptin is strongly dependent on growth and luteinizing hormones, which play an important role in the brain-pituitary axis. The concentration of leptin in blood plasma increases with age and obesity and is associated with the level of leptin mRNA in adipose tissue. Selection of appropriate internal control gene (ICG) for normalization of quantitative PCR data for genes of interest is critical for interpretation of results. The estimation of leptin mRNA is important in the research on regulation of feed intake and metabolic and energy balance. Therefore, the objective of this study was to evaluate the stability of mRNA expression for a number of candidate housekeeping genes in the porcine backfat tissue across different breeds. In our study we used a freeware computer program (geNorm) to evaluate the most stable among eight ICG genes (β-actin, hypoxanthine phosphoribosyltransferase 1, TATA binding protein, glyceraldehyde-3-phosphate dehydrogenase, ornithine decarboxylase antizyme 1, 60S ribosomal protein L27, 40S ribosomal protein S29, eukaryotic elongation factor (1) in 90 mRNA samples of backfat tissue. In the study we used three breeds differing in muscling: Polish Large White (n = 30), Polish Landrace ( n = 30) and Pietrain ( n = 30). The results showed that the three most stable genes were ornithine decarboxylase antizyme 1 (OAZ1), 60S ribosomal protein L27 (RPL27) and β-actin ( M = 0.579, 0.602 and 0.607, respectively). In order to evaluate the abundance of leptin mRNA, the two most stable genes were used. The highest level of mRNA expression was obtained for PL and the lowest for Pietrain pigs. These results confirmed previous studies which showed that pigs with lean carcass were characterized by a lower level of leptin transcript compared to pigs with large fat deposit. Moreover, we analyzed relationship between C3469T Lep polymorphism and level of leptin mRNA, but did not find significant associations. Our study provides a new panel of housekeeping genes for normalization of the expression of a gene of interest in adipose tissue.

Genetic deficiency for proprotein convertase subtilisin/kexin type 2 in mice is associated with decreased adiposity and protection from dietary fat-induced body weight gain

Proprotein convertase subtilisin/xexin type 2 (PCSK2) is an endoproteinase responsible for proteolytic activation of a number of precursors to active neuropeptides and peptide hormones, known to influence glucose homeostasis, food intake and ultimately body mass. In this study, we examined the consequences of PCSK2 deficiency on these phenotypic traits. Weight gain with age under diets of different fat contents was monitored. White adipose tissue (WAT) and muscle masses were evaluated. Plasma levels of triglycerides, leptin, ghrelin, insulin and proglucagon-derived peptides were measured as well as leptin and acetyl coenzyme-α carboxylase (ACCα) mRNA levels in adipose tissue. Compared with their Pcsk2 (+/+) littermates, Pcsk2 (-/-) mice weighed significantly less as weanlings and as adults. As adults, they carried noticeably less fat mass, with similar lean muscle mass: their plasma leptin level and adipose tissue leptin mRNA level were accordingly lower. PCSK2 deficiency did not affect food intake or the level of the orexigenic hormone ghrelin. However, PCSK2 deficiency resulted in decreased plasma triglycerides and reduced ACCα mRNA levels in WAT. Interestingly, unlike their Pcsk2 (+/+) littermates, Pcsk2 (-/-) were resistant to enhanced body weight gain when fed a high-fat diet. Consistent with a role of PCSK2 in body mass gain, diet-induced or genetically obese mice were found to contain significantly higher levels of PCSK2 mRNA in their brain and stomach than their lean counterparts. Collectively, these results suggest that PCSK2 contributes to increase in body mass through the various regulatory peptides generated through its action. It represents a potential target in the prevention and treatment of obesity.

High‐fat diet induced obesity accelerates colon tumor formation in AJ and ICR mice

Recent studies have indicated that the risk of colorectal cancer is associated with overweight and obesity. The objective of this study was to determine the effect of high fat diet induced obesity on the incidence of AOM/DSS‐induced colon carcinogenesis and to elucidate possible mechanisms. Strain‐specific responses were studied using A/J and ICR mice. Study results indicated the tumor numbers in animals fed high fat diet were significantly higher than those of the animals on low‐fat diet. The concentrations of adipose tissue related serum factors including leptin, insulin and IGF‐1 were elevated in obese animals indicating these are one of the possible signals to facilitate colon tumor formation. The expressions of leptin mRNA in adipose tissue and leptin receptor(ObR) mRNA in colon tissue were significantly higher in obese mice compared to those in lean mice only in AJ stain. The protein expressions of ObR, IR, p‐Akt, p‐ERK, Bcl‐xl and cyclin D1 were higher in obese animals than those in lean animals for both strains. These results imply adipose tissue related hormonal factors contribute to colon tumor growth. Strain‐specific responses are also suggested. This study was supported by the SRC program of the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (2009‐0063409 and R01‐2008‐000‐20708‐0).Grant Funding Source: Nutrition(ASN)

Effect of exercise training on adipocyte-size-dependent expression of leptin and adiponectin

Aims Our aim was to evaluate the effect of exercise training (TR) on adipocyte-size-dependent expression of leptin and adiponectin. Main methods Male Wistar rats were divided into 2 groups, sedentary control (CR) and TR group, and both monitored for 9 weeks. Adipocytes isolated from epididymal, retroperitoneal, and inguinal fat depots were independently separated into 3 fractions of different cell size, and the relationships between adipocyte size and either leptin or adiponectin mRNA were determined by real-time RT-PCR analysis. Key findings In epididymal and inguinal adipose tissue, positive relationships between adipocyte size and both leptin and adiponectin mRNA expression were found. Comparison of TR and CR rats showed no significant effect of TR on the slopes of the linear regression lines of correlation between leptin mRNA and adipocyte size in either adipose tissue, whereas the slopes of the regression line of correlation between adipocyte size and adiponectin mRNA were greater in TR group. Leptin levels per milliliter of plasma were significantly lower in TR than CR rats, whereas leptin levels adjusted to the 3 fat depots did not differ. TR did not affect adiponectin levels in plasma, whereas adiponectin levels adjusted to the 3 fat depots were significantly greater in TR than CR group. Significance TR-induced reduction in leptin mRNA expression was closely associated with smaller adipocyte size. However, TR amplified the adipocyte-size-dependent expression of adiponectin mRNA, suggesting that TR-induced alterations in adiponectin mRNA may also be mediated by factor(s) other than adipocyte size.

Development of high‐fat‐diet‐induced obesity in female metallothionein‐null mice

Oxidative stress accelerates adipocyte differentiation and lipid accumulation, leading to endoplasmic reticulum (ER) stress, which causes insulin resistance. Because metallothionein (MT) has a role in prevention of oxidative and ER stress, we examined the effects of MT on the development of obesity induced by 27 wk of a high-fat diet (HFD) in female MT-I- and MT-II-null (MT(-/-)) and wild-type (MT(+/+)) mice. Body weight, fat mass, and plasma cholesterol increased at a greater rate in MT(-/-) mice fed an HFD than in MT(-/-) mice fed a control diet (CD) and MT(+/+) mice fed an HFD, indicating that MT(-/-) mice fed an HFD became obese and hypercholesterolemic and that MT could prevent HFD-induced obesity. The observed increases in the levels of plasma leptin and leptin mRNA in the white adipose tissue of MT(-/-) mice fed the HFD suggested a leptin-resistant state. Enhanced expression of a mesoderm-specific transcript, which regulates the enlargement of fat cells, was accompanied by enlarged adipocytes in the white adipose tissue of young MT(-/-) mice before obesity developed after 3 and 8 wk of feeding the HFD. Thus, MT may have a preventive role against HFD-induced obesity by regulating adipocyte enlargement and leptin signaling.

Leptin mRNA and Protein Immunoreactivity in Adipose Tissue and Liver of Rainbow Trout (Oncorhynchus mykiss) and Immunohistochemical Localization in Liver

Leptin is an important modulator of energy balance and metabolism in mammals, but for evolutionary older vertebrates like fish, the first reports on leptin expression were only recently characterized and the functional role scarcely. In this study, we demonstrated leptin immunoreactivity in liver tissue of rainbow trout (Oncorhynchus mykiss) by immunohistochemistry using three different polyclonal antibodies against mammalian leptin. Immunoreactivity was observed in hepatocytes and also in parts of the biliary system. Using Western blot, we detected an immunoreactive band of about 16 kDa in serum and visceral adipose tissue (AT) of rainbow trout. The presence of leptin in fish AT has been doubted in other studies. Besides the immunoreactivity, leptin mRNA was detected in trout AT albeit not in all animals sampled. Our observations add further evidence to the concept of AT being a source of leptin in trouts. Moreover, the cellular localization of leptin immunoreactivity in liver opens up new vistas for understanding the functional role of leptin in teleosts.

Lysine restriction and realimentation affected growth, blood profiles and expression of genes related to protein and fat metabolism in weaned pigs

To investigate the effects of lysine restriction and subsequent realimentation on growth performance, blood profiles and gene expression of leptin and myostatin, 128 weaned pigs [initial body weight (BW) 6.96 ± 1.07 kg, 26 ± 2 days of age] were randomly allotted to four treatments. The starter diets during the first 2 weeks (P1) contained 100%, 80%, 70% or 60% of recommended lysine levels (National Research Council, 1998). Then, common grower 1 and 2 diets were offered for 2 weeks (P2 and P3) each. During P1, average daily gain (ADG) was linearly reduced (p < 0.05) with the increasing levels of lysine restriction. Growth rate was greater in pigs previously fed lysine-restricted diets than well-fed pigs although it did not reach a significant level during realimentation. However, the final BW and overall ADG were the lowest (p < 0.05) and F/G was poor in pigs fed 60% lysine diet. Relative visceral organ weights and composition of skeletal muscle were similar (p > 0.05) among the treatment. Blood triglyceride and glucose levels were increased (p < 0.05) during P1, while blood urine nitrogen, total protein and albumin levels were decreased (p < 0.05) during P2 with the reduction in dietary lysine levels. The abundance of myostatin mRNA in skeletal muscle and leptin mRNA in subcutaneous adipose tissue were lower (p < 0.05) in lysine-restricted pigs than in pigs fed non-restricted diets. In conclusion, 80% and 70% lysine restriction of starter diets resulted in inferior growth and compensatory growth effect was noted during realimentation, while 60% lysine restriction had a negative influence on growth performance. Moreover, the changes in myostatin and leptin mRNA abundance caused by nutritional manipulations may be involved in the regulation of protein and fat deposition in young pigs.

Effects of a high‐fat, low‐ versus high‐glycemic index diet: retardation of insulin resistance involves adipose tissue modulation

Beneficial effects of low glycemic index (GI) diets in rodents have been studied using healthy low-fat diets, while the effects might be different on high-fat diets inducing progression of insulin resistance. We fed C57BL/6J male mice high-fat low/high-GI (LGI/HGI) diets for 13 wk. Glucose and insulin tolerance and serum substrates, including adipokines, were measured longitudinally. The LGI group showed a significantly higher glucose tolerance from wk 2 onwards, which was supported by lower serum insulin and free fatty acids levels at 8 wk, and a tendency for lower leptin levels, while resistin levels remained similar. At 11 wk, when differences in serum resistin started to increase, differences in serum insulin were diminished. Although food intake was similar throughout the study, body weights and epididymal adipose tissue mass became significantly lower in the LGI group at necropsy. Several serum substrates and adipose tissue leptin mRNA levels, as analyzed by Q-PCR, were, again, significantly lower, whereas adiponectin mRNA levels were higher. Taken together, an LGI high-fat diet maintains higher glucose tolerance and insulin sensitivity via adipose tissue modulation solely because of a difference in the type of carbohydrate, supporting a nutritional approach in the fight against insulin resistance.

Early Undernutrition Leads to Long-Lasting Reductions in Body Weight and Adiposity Whereas Increased Intake Increases Cardiac Fibrosis in Male Rats1,

Previous studies suggest that both overfeeding and undernutrition during development increase the risk of obesity and hypertension in adulthood. In this study, we examined both short- (24 d) and long- (16 wk) term effects of early postnatal over- and underfeeding in rats on body weight, body composition, plasma hormones, adiposity markers, and hypothalamic neuropeptide Y content. Cardiovascular changes were also examined by measuring blood pressure and cardiac fibrosis. Rats raised in litters of 3, 12, or 18 pups per mother were used to model early onset overfeeding, control, and underfeeding, respectively. At 24 d of age, pups raised in small litters (SL) were 10% heavier than pups from normal litters, accompanied by increased organ mass and fat mass, elevated plasma leptin, corticosterone, and uncoupling protein-1 mRNA in brown adipose tissue. On the other hand, pups raised in large litters were 17% lighter with no significant changes in plasma leptin. Overfeeding during the first 3 wk of life led to increased plasma leptin concentration in adulthood, whereas underfed rats remained significantly lighter throughout the study, with no evidence of catch-up growth. Rats raised in SL were more susceptible to developing cardiac fibrosis with a 22% increase in collagen deposition compared with control rats at 16 wk of age (P < 0.05). This was independent of any changes in blood pressure. This study demonstrates that nutritional changes early in postnatal development can have long-lasting effects on body weight, adiposity, and some mediators involved in energy homeostasis and can also lead to structural changes in the heart in adulthood. This highlights the importance of identifying potential early life risk factors involved in the modulation of childhood nutrition.

Leptin and cardiovascular disease: response to therapeutic interventions.

Leptin and cardiovascular disease: response to therapeutic interventions.