Leptin In Rats Research Articles

Long‐term exposure to incense smoke alters metabolism in Wistar albino rats

The burning of incense is an important source of indoor air pollution in Asia. We assessed the effect of long-term exposure to incense smoke on the body weight and levels of circulating glucose, triglycerides, total cholesterol, HDL-cholesterol, insulin, adiponectin and leptin in Wistar albino rats. Two groups of rats were used. First group (n = 12) was exposed daily to incense smoke for 4 months at the rate of 4 g day(-1) in the exposure chamber. Another group of rats (n = 12), was used as non-exposed control. Blood samples were collected from all animals after 4, 8, 12 and 16 weeks of exposure. Serum glucose, triglycerides, total cholesterol and HDL-cholesterol, LDL-cholesterol insulin, adiponectin and leptin were measured. Our results showed that incense smoke exposure was associated with decreased weight gain and the adverse metabolic changes of increased triglycerides and decreased HDL-cholesterol concentrations. Exposure to incense was also associated with a transient increase of leptin levels. Taken together, these data suggest that incense smoke influences metabolism adversely in rats. The effect of incense smoke on human health and the underlying mechanisms need to be studied further.

Corrigendum

CorrigendumCorrigendumPublished Online:01 Feb 2011https://doi.org/10.1152/ajpendo.zh1-6178-corr.2011Original articleMoreSectionsPDF (407 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Volume 299, December 2010Perello M, Çakir I, Cyr NE, Romero A, Stuart RC, Chiappini F, Hollenberg AN, Nillni EA. Maintenance of the thyroid access during diet-induced obesity in rodents is controlled at the central level; doi:; http://ajpendo.physiology.org/cgi/content/full/299/6/E976.In this article, the wrong Western blot image was placed above the bar graph in Fig. 2C (it was actually the same image that was used in Fig. 2B). A full, revised version of Fig. 2, with the corrected Western blot image, is shown here.Fig. 2.The change in the set point of the hypothalamic-pituitary-thyroid (HPT) axis of DIO rats correlates with plasma leptin and with an increase of pSTAT3 signaling within TRH neurons. A: correlation between serum leptin and serum tiiodothyronine (T3) in lean and DIO rats (r = 0.46 and 0.66 for lean and DIO rats, respectively). Each point represents a measurement from a single animal. B and C: thyroid hormone receptor-β2 (TRβ2) and leptin receptor (ObRb) protein levels were similar in both groups of rats. To perform this, hypothalamic paraventricular nuclei (PVN) were removed from fed lean and DIO rats; proteins were extracted in RIPA lysis buffer, and TRβ2 (60 kDa), ObRb (120 kDa), and β-actin (43 kDa) levels were assayed by Western blot. In addition, brain sections of fed rats were subjected to double immunohistochemistry using anti-pSTAT3 (brown staining) and anti-pro-TRH (red fluorescent staining) antiserum. D: low-magnification images for each individual staining for each group and high-magnification merged images. Arrows point to dual-labeled cells. Scale bars, 50 (low magnification) and 20 μm (high magnification). E: bar graph of the quantitative analysis of the percentage of TRH neurons positive for pSTAT3 in the PVN of fed lean and DIO rats (n = 3 and 5/group). Values are means ± SE. *P < 0.05 vs. lean group.Download figureDownload PowerPointThis article has no references to display. Download PDF Previous Back to Top FiguresReferencesRelatedInformation Collections Related ArticlesMaintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level 01 Dec 2010American Journal of Physiology-Endocrinology and Metabolism More from this issue > Volume 300Issue 2February 2011Pages E422-E422 Copyright & PermissionsCopyright © 2011 the American Physiological Societyhttps://doi.org/10.1152/ajpendo.zh1-6178-corr.2011History Published online 1 February 2011 Published in print 1 February 2011 Metrics

Region-specific diet-induced and leptin-induced cellular leptin resistance includes the ventral tegmental area in rats

Diet-induced obesity (DIO) results in region-specific cellular leptin resistance in the arcuate nucleus (ARC) of the hypothalamus in one strain of mice and in several medial basal hypothalamic regions in another. We hypothesized that the ventral tegmental area (VTA) is also likely susceptible to diet-induced and leptin-induced leptin resistance in parallel to that in hypothalamic areas. We examined two forms of leptin resistance in F344xBN rats, that induced by 6-months of high fat (HF) feeding and that induced by 15-months of central leptin overexpression by use of recombinant adeno-associated viral (rAAV)-mediated gene delivery of rat leptin. Cellular leptin resistance was assessed by leptin-stimulated phosphorylation of signal transducers and activators of transcription 3 (STAT3) in medial basal hypothalamic areas and the VTA. The regional pattern and degree of leptin resistance with HF was distinctly different than that with leptin overexpression. Chronic HF feeding induced a cellular leptin resistance that was identified in the ARC and VTA, but absent in the lateral hypothalamus (LH), ventromedial hypothalamus (VMH), and dorsomedial hypothalamus (DMH). In contrast, chronic central leptin overexpression induced cellular leptin resistance in all areas examined. The identification of leptin resistance in the VTA, in addition to the leptin resistance in the hypothalamus, provides one potential mechanism, underlying the increased susceptibility of leptin resistant rats to HF-induced obesity.

Aging effects on exercise-induced alternations in plasma acylated ghrelin and leptin in male rats

Ghrelin and exercise have been known to stimulate the release of growth hormone which is related to the glucose metabolism. However, the age effects of exercise on ghrelin in energy consumption remain unclear. Young (3month old) and middle-aged (12month old) Sprague-Dawley male rats were overnight fasted, and then randomly partitioned into exercise and control groups. Exercise groups swam for 20min in 25°C water. Rats immersed in 25°C water for 20min were used as control animals. All blood samples were collected before and 10, 20, 30, and 60min after initiation of exercise via the right jugular vein. Our results indicated that the swimming regimen decreased the secretion of acylated ghrelin and insulin, but increased the secretion of leptin, lactate, and glucose. In addition, exercise significantly amplified the inverse correlation between leptin and acylated ghrelin (r<-0.6) in middle-age group. Both the above findings were not emphasized in related articles before. Moreover, the time courses of these changes were slightly different in young and middle-aged rats. In basal metabolic characteristics, body weight and the plasma lactate, glucose, insulin, and leptin are higher in middle-age group than that in young group. In conclusion, compared with young rats, middle-aged rats have higher basal body weight, plasma glucose, insulin, and leptin, but age had no effect on the level of plasma acylated ghrelin. A 20-min exercise regimen decreased acylated ghrelin and increased leptin with inverse correlation between them which was strengthened during exercise, but were not influenced by age.

Impact of Obesity and Leptin on Protein Expression Profiles in Mouse Colon

Elevated leptin levels in obesity are associated with increased risk of colon pathology, implicating leptin signaling in colon disease. However, leptin-regulated processes in the colon are currently uncharacterized. Previously, we demonstrated that leptin receptors are expressed on colon epithelium and that increased adiposity and elevated plasma leptin in rats are associated with perturbed metabolism in colon tissue. Thus, we hypothesize that obesity disrupts expression of proteins regulated by leptin in the colon. A proteomic analysis was conducted to investigate firstly, differences in the colon of mice lacking leptin and leptin signaling (ob/ob and db/db, respectively) by comparing protein expression profiles with wild-type mice. Secondly, responses to leptin challenge in wild-type mice and ob/ob mice were compared to identify leptin-regulated proteins and associated cellular processes. Forty proteins were identified with significantly altered expression patterns associated with differences in leptin status in comparisons between all groups of mice. These proteins are associated with calcium binding, cell cycle, cell proliferation, electron transport chain, energy metabolism, protein folding and transport, redox regulation, structural proteins, and proteins involved in transport and regulation of mucus production. This study provides evidence that obesity and leptin significantly alter protein profiles of a number of proteins linked to cellular processes in colon tissues that may be linked to the increased risk of colon pathology associated with obesity.

Serum Leptin, Adiponectin and Tumor Necrosis Factor-α in Hyperlipidemic Rats with/without Concomitant Diabetes Mellitus

We compared the lipid profiles and serum levels of leptin, adiponectin and tumor necrosis factor-α (TNF-α) in rats with/without hyperlipidemia and with/without concomitant diabetes mellitus. Forty 10-wk-old male Wistar rats were divided into four groups. Groups A and C received standard food for 12 wks. Groups B and D received a high-fat diet enriched with 2% additional cholesterol. Moreover, insulin-deficient (type I) diabetes mellitus was induced in rats in groups C and D with intraperitoneal injections of streptozotocin. Fasting serum leptin levels were decreased in diabetic groups (groups C and D) compared with controls. Fasting serum adiponectin levels were decreased in groups C and D compared with group A. Serum TNF-α levels were augmented in groups B and D, those fed with an atherogenic diet. By contrast, TNF-α levels were decreased in group C. Our data suggest that serum leptin, adiponectin and TNF-α levels may serve as markers of obesity and type I diabetes mellitus.

Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by leptin

Leptin is not only a feedback modulator of feeding and energy expenditure but also regulates reproductive functions, CNS development and mood. Obesity and major depression are growing public health concerns which may derive, in part, from disregulation of leptin feedback at the level of the hypothalamic feeding centers and mood regulators within the limbic system. Identifying downstream mediators of leptin action may provide therapeutic opportunities. We and others have previously reported that thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH 2) and TRH-like peptides (pGlu-X-Pro-NH 2, where “X” can be any amino acid residue) have neuroprotective, antidepressant, anti-epileptic, analeptic, anti-ataxic, and anorectic properties. For this reason, young, adult male Sprague–Dawley rats were injected ip with 1 mg/kg rat leptin and peptide and protein levels were measured in brain and peripheral tissues at 0, 0.5, 1 and 2 h later. Eleven brain regions: pyriform cortex (PYR), entorhinal cortex (ENT), cerebellum (CBL), nucleus accumbens (NA), frontal cortex (FCX), amygdala (AY), posterior cingulate (PCNG), striatum (STR), hippocampus (HC), medulla oblongata (MED) and anterior cingulate (ACNG) and five peripheral tissues (adrenals, testes, epididymis, pancreas and prostate) were analyzed. TRH and six TRH-like peptide levels in STR fell by 0.5 h consistent with leptin-induced release of these peptides: STR (7↓). Significant changes in TRH and TRH-like peptide levels for other brain regions were: CBL (5↓), ENT (5↓), HC (4↓), AY (4↓), FCX (3↓), and ACNG (1↓). The rapid modulation of TRH and TRH-like peptide release combined with their similarity in behavioral, neuroendocrine, immunomodulatory, metabolic and steroidogenic effects to that of leptin is consistent with these peptides participating in downstream signaling.

Sensitivity to the Anorectic Effects of Leptin Is Retained in Rats Maintained on a Ketogenic Diet despite Increased Adiposity

Background: Rats maintained on a ketogenic diet (KD; 80% fat, 15% protein, 5% carbohydrate) have increased adiposity and leptin as compared to chow-fed controls (CH; 16% fat, 19% protein, 65% carbohydrate), although body weights and daily caloric intakes do not differ. Methods: Rats maintained on a KD or CH were assessed for responsivity to intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) leptin. Hypothalamic gene expression was evaluated to determine the effects of KD on proopiomelanocortin (POMC) mRNA expression and components of the leptin-signaling system. Results: Caloric intake by KD rats was decreased at a lower dose of i.p. leptin (100 µg) than was required to reduce intake by CH rats (leptin, caloric intake was reduced in KD rats as compared to intake following i.p. saline; p < 0.05). In a separate experiment to evaluate responsivity to i.c.v. leptin, the minimal dose of leptin required to significantly reduce 24-hour caloric intake did not differ between the groups. In the arcuate nucleus, POMC mRNA was elevated after a lower dose of i.c.v. leptin in KD rats (5 µg) than was required to increase POMC mRNA expression in CH rats (15 µg) or reduce caloric intake in either group. Finally, evaluation of the level of phosphorylated STAT3 (pSTAT3) in the arcuate and SOCS3 mRNA in the hypothalamus revealed significantly more pSTAT3-positive cells and increased SOCS3 mRNA expression at baseline for KD rats, compared to CH, neither of which was further increased following i.p. leptin administration. Conclusion: These data demonstrate that despite increased adiposity, leptin and markers of leptin resistance, responsivity to the anorectic effects of exogenous leptin is retainable during maintenance on a KD.

Modulation of hypothalamic PTP1B in the TNF-α-induced insulin and leptin resistance

We have associated functional and molecular studies of insulin and leptin to investigate the effect of TNF-α on central insulin and leptin signaling in rats pre-treated with PTP1B-ASO. The icv infusion of TNF-α-induced an increase in PTP1B protein expression and activity, and attenuated insulin and leptin sensitivity and signaling in the hypothalamus. However, TNF-α was able to completely blunt the leptin and insulin effect in rats treated with PTP1B-ASO, suggesting that TNF-α does not require PTP1B to fully attenuate the leptin and insulin effects. In addition, our data also show that other mechanisms of insulin and leptin resistance are activated in the hypothalamus by TNF-α.

Effects of Dietary Beef and Chicken With and Without High Amylose Maize Starch on Blood Malondialdehyde, Interleukins, IGF-I, Insulin, Leptin, MMP-2, and TIMP-2 Concentrations in Rats

Dietary red and processed meats may increase risk of colorectal cancer (CRC), whereas fiber may be protective. Recently, we demonstrated that dietary beef causes greater colonic DNA strand breakage than equivalent levels of chicken in rats and that resistant starch (RS) as 20% high amylose maize starch (HAMS) attenuated the damage. From that study, we now report measures of circulating factors that may influence CRC initiation or progression including malondialdehyde (MDA), leptin, insulin-like growth factor-I (IGF-I), insulin, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of MMP-2 (TIMP-2), interleukins (IL), and short chain fatty acids. MDA levels were increased by beef diets relative to the chicken diets. Leptin concentrations, which were lower for chicken than beef at the 35% level in the absence of HAMS, were lowered by HAMS. Higher dietary chicken (but not beef) increased IGF-I irrespective of HAMS feeding. Higher levels of chicken resulted in greater insulin concentrations than for beef in rats fed HAMS. Without dietary HAMS, TIMP-2 concentration increased in response to both meats but was highest for chicken. MMP-2 and TIMP-2 concentrations were higher for HAMS diets. IL-1β and IL-12 concentrations were lowered by HAMS feeding. Colonic DNA strand breakage was positively associated with circulating leptin and MDA concentrations as well as tissue MDA concentrations and negatively associated with plasma TIMP-2 concentration. MMP-2 and TIMP-2 positively correlated with hepatic portal butyrate levels but leptin concentrations correlated negatively. These results suggest diets high in meat or RS could influence cancer initiation or progression by changes in circulating levels of hormones and other factors.

Effects of chronic fructose feeding on leptin sensitivity and obesity in mice

Chronic 60% fructose feeding decreases the sensitivity to leptin in rats as assessed by decreases in food intake and body weight after administration of exogenous leptin. We hypothesized that a 60% fructose diet would also lead to leptin resistance in mice, as assessed by 1) a lack of response to exogenous leptin, 2) elevated circulating leptin, and 3) a lack of entry into torpor upon fasting. Male Hsd:NSA(CF‐1) mice were fed either a 60% fructose diet or an isocaloric fructose‐free diet and food intake and body weight were monitored. After 4 weeks of the diet, mice were injected intraperitoneally with leptin (5 mg/kg) and consequent changes in food intake and body weight were monitored. After 8 more weeks on the diet, plasma leptin levels were measured, and then mice were fasted at 20°C for 24 hours. The two feeding groups had similar caloric intake and gained the same amount of weight over the 12 week feeding period. Additionally, high fructose feeding did not attenuate the decrease in either food intake or body weight in response to exogenous leptin. Further, mice on the high fructose diet showed no difference in circulating leptin from mice on the fructose‐free diet (22.9±6.3 and 24.4±3.2 ng/ml, respectively). Finally, neither feeding group entered torpor when fasted at 20°C. These observations indicate the failure of a 60% fructose diet to induce leptin resistance in Hsd:NSA(CF‐1) mice over 12 weeks.

Protective effect of the endothelin antagonist CPU0213 against isoprenaline-induced heart failure by suppressing abnormal expression of leptin, calcineurin and SERCA2a in rats

Heart failure (HF) may be produced by sustained beta-adrenoceptor stimulation by causing changes in the expression of endothelin-1 (ET-1), the leptin system, calcineurin and sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) underlying cardiac dysfunction. The aim of this study was to verify whether isoprenaline (ISO)-induced HF is attributed to changes in the above molecular markers, and whether the dual ET-receptor antagonist CPU0213 could reverse the cardiac dysfunction caused by ISO treatment, focusing on these molecular markers. HF was induced in rats by administration of ISO (2 mgkg(-1) s.c.) for 10 days. CPU0213 (30 mgkg(-1) s.c.) and propranolol (4 mgkg(-1) s.c.) were administered on days 7-10. HF developed after 10 days' ISO administration and was manifest as impaired cardiac performance, increased heart weight index, oxidative stress, elevated serum enzymes, and disordered expression of the endothelin system, leptin system, calcineurin and SERCA2a. All these abnormalities were significantly reversed by CPU0213, and the effectiveness of this ET-receptor antagonist was comparable to that of propranolol. Thus, antagonism of ET receptors by CPU0213 normalizes these changes in molecular markers, alleviating HF.

Adenovirus‐Mediated Leptin Expression Normalises Hypertension Associated with Diet‐Induced Obesity

In our previous study, moderate increases in plasma leptin levels achieved via administration of recombinant adenovirus containing the rat leptin cDNA were shown to correct the abnormal metabolic profile in rats with diet-induced obesity, suggesting that these animals had developed resistance to the metabolic effects of leptin, which could be reversed by leptin gene over-expression. However, the effect of this therapeutic strategy on blood pressure was not investigated. The present study aimed to determine whether a moderate increase of endogenous plasma leptin levels affected arterial blood pressure in rats with diet-induced obesity and hypertension. The major finding from the present study was that the natural rise in plasma leptin with weight-gain is insufficient to counterbalance high blood pressure associated with obesity, additional increases of circulating leptin levels with adenoviral leptin gene therapy led to normalisation of blood pressure in high-fat diet-induced obese and hypertensive rats. Mechanistically, the reduction of blood pressure by leptin in obese rats was likely independent of alpha-adrenergic and acetylcholinergic receptor mediation. This is the first study to demonstrate that further increases in circulating leptin levels by leptin gene transfer during obesity could reduce blood pressure.

Metabolic programming of lipid profile and reproductive organs weight by leptin treatment on early life

To evaluate whether the neonatal leptin treatment during the first days of life can program the male reproductive organs weight and the lipid profile. At birth 6 dams were divided into 2 groups: Leptin - each pup was injected with 50microL of recombinant rat leptin (80ng/g BW, sc), for the first 10 d of lactation; Control - each pup received the same volume of saline. After weaning, all pups received unlimited access to food until 190 days of age when they were killed. Values are given as mean + or - SEM of 6 animals and Test t Student was used to analyze the results. The leptin treatment resulted in a significant increase in body weight (Control= 411.8 + or - 16.31; Leptin= 481.8 + or - 11.29, p=0.005) and food consumption (Control= 25.32 + or - 0.09; Leptin= 32.42 + or - 0.15, p=0.0001) and a significant reduction in triglycerides levels (Control= 540.0 + or - 117.9; Leptin= 93.25 + or - 15.21, p=0.006) and in the weight of hypothalamus (Control= 0.234 + or - 0.016; Leptin= 0.154 + or - 0.015, p=0.007), pituitary (Control= 0.104 + or - 0.0120; Leptin= 0.033 + or - 0.012, p=0.003), testis (Control= 3.75 + or - 0.055; Leptin= 3.19 + or - 0.10, p=0.002) and prostate (Control=1.641 + or - 0.1389; Leptin= 0.91 + or - 0.07, p=0.001). Leptin treatment on the first days of life can program the reproductive organs weight and the lipid profile of the progeny.

Leptin reduces plasma ANP level via nitric oxide-dependent mechanism

Leptin is a circulating adipocyte-derived hormone that influences blood pressure (BP) and metabolism. This study was designed to define the possible role of leptin in regulation of the atrial natriuretic peptide (ANP) system using acute and chronic experiments. Intravenous infusion of rat leptin (250 microg/kg injection plus 2 microg.kg(-1).min(-1) for 20 min) into Sprague-Dawley rats increased BP by 25 mmHg and decreased plasma level of ANP from 80.3 +/- 3.45 to 51.8 +/- 3.3 pg/ml. Reserpinization attenuated the rise in BP, but not the reduction of plasma ANP during leptin infusion. N(omega)-nitro-l-arginine methyl ester prevented the effects of leptin on the reduction of ANP level. In hyperleptinemic rats that received adenovirus containing rat leptin cDNA (AdCMV-leptin), BP increased during first 2 days and then recovered to control value. Plasma concentration of ANP and expression of ANP mRNA, but not of atrial ANP, in hyperleptinemic rats were lower than in the control groups on the first and second week after administration of AdCMV-leptin. These effects were not observed by the pretreatment with N(omega)-nitro-l-arginine methyl ester. No differences in renal function and ANP receptor density in the kidney were found between hyperleptinemic and control rats. Basal ANP secretion and isoproterenol-induced suppression of ANP secretion from isolated, perfused atria of hyperleptinemic rats were not different from those of other control groups. These data suggest that leptin inhibits ANP secretion indirectly through nitric oxide without changing basal or isoproterenol-induced ANP secretion.

Influence of Weitongxiaopi Decoction on serum and gastric ghrelin and leptin in rats with functional dyspepsia

Influence of Weitongxiaopi Decoction on serum and gastric ghrelin and leptin in rats with functional dyspepsia

Vitamin E regulates adipocytokine expression in a rat model of dietary-induced obesity

The aim of this study was to determine the effect of the antioxidant vitamin E (VE) on adiponectin and leptin expression in obese rats. Thirty weaning male Sprague-Dawley rats were divided into three groups as follows: (1) a control group, fed with normal chow; (2) a diet-induced obesity group (DIO), fed with a high-fat diet and (3) an intervention group, fed with a high-fat diet supplemented with VE (350 mg/kg). After 10 weeks of being fed according to these group assignments, rats were weighed and euthanized. Blood and adipose tissues were then immediately collected; mRNA and protein levels of leptin and adiponectin were measured by realtime reverse transcription-polymerase chain reaction and Western blotting. Biomarkers of oxidative stress, including serum levels of 8-epi-prostaglandin-F(2)alpha (8-epi-PGF(2)alpha) and glutathione peroxidase activity, were also examined. Adiponectin and leptin levels were lower in the DIO group than in the control group. VE intervention increased the expression of both leptin and adiponectin (P values < 0.05). Association analysis showed that serum leptin levels correlated positively with body fat mass (r = 0.601, P < 0.05). Both serum leptin and adiponectin levels were associated with the presence of serum 8-epi-PGF2 alpha (leptin, r = 0.513, P < 0.05; adiponectin, r = -0.422, P < 0.05). Administration of VE decreases leptin and adiponectin expression in obese rats. This finding is consistent with the view that antioxidants can play an important role in the treatment of obesity-related diseases.

구기엽 에탄올 추출물이 고지방 식이 유도 비만쥐의 비만과 혈중 생화학적 지표 조절에 미치는 영향

Dept. of Food and Nutrition, Kangwon National University, Gangwon 245-711, KoreaAbstractThis study was conducted to investigate the effects of ethanol extract from Lycii folium (L. folium) leaves on obesity index, serum lipids, homocysteine, leptin, ghrelin, and glucose in obese rats. Sprague-Dawley rats were administrated high-fat diets to induce obesity. Then, obese rats were divided into three diet groups: a basal-diet obese group (BO group), high-fat diet obese group (FO group), and high-fat diet plus L. folium extract obese group (FLEO group). Three groups were each fed experimental diet for 8 weeks. There were no significant differences in body weight and FER among the groups. However, obesity index such as Rohrer index, Lee index, and T.M. index of FLEO group was significantly decreased as compared to FO group. While serum triglyceride of BO group was significantly decreased as compared to FO group, there were no significant differences in serum lipids, homocysteine, leptin, ghrelin and glucose between FLEO group and FO group. In conclusion, these results indicated that ethanol extract from L. folium leaves might be beneficial with anti-obese effect by reduction of obesity indices in obese rats. Key words: Lycii folium, lipids, homocysteine, leptin, ghrelin, obese, rats

Effects of emodin on cell apoptosis of intestinal mucosa and serum leptin in rats with severe acute pancreatitis

To explore the mechanisms of emodin in protecting intestinal mucosal barrier in rat with severe acute pancreatitis (SAP). Sixty SD rats were randomly divided into three groups: sham-operation group, untreated group, and emodin group. SAP in rats of the untreated group and the emodin group was induced by retrograde pumping of 3.0% sodium cholate to the common bile duct. Specimens were obtained 24 hours after the severe acute pancreatitis was induced. Serum level of leptin, serum activity of amylase and plasma content of endotoxin were measured. Ileum mucosa from ileocecal junction was observed by light microscopy and electron microscopy to measure pathological and ultrastructural changes. Apoptosis of ileum mucosal cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method, and expression of Bax in ileum mucosal cells was measured by immunohistochemical method. Compared with the sham-operation group, there was significant increase in the levels of leptin, endotoxin, the activity of amylase, apoptosis index and Bax expression in the untreated group (P<0.01). Compared with the untreated group, the level of endotoxin, apoptotic index and Bax expression level in the emodin group were significantly reduced (P<0.01) and the leptin level was increased (P<0.05). More severe pathological changes appeared in the untreated group than in the sham-operation group under the light and electron microscopes; meanwhile less severe damage was observed in the emodin group as compared with the untreated group. Emodin can inhibit the apoptosis of intestinal mucosa cells and up-regulate the serum leptin content to protect the intestina1 barrier function and prevent the translocation of bacteria and endotoxin.

Differential effects of leptin receptor mutation on male and female BBDR.Gimap5−/Gimap5− spontaneously diabetic rats

Rodents homozygous for autosomal leptin receptor gene mutations not only become obese, insulin resistant, and hyperleptinemic but also develop a dysregulated immune system. Using marker-assisted breeding to introgress the Koletsky rat leptin receptor mutant (lepr-/lepr-), we developed a novel congenic BBDR.(lepr-/lepr-) rat line to study the development of obesity and type 2 diabetes (T2D) in the BioBreeding (BB) diabetes-resistant (DR) rat. While heterozygous lepr (-/+) or homozygous (+/+) BBDR rats remained lean and metabolically normal, at 3 wk of age all BBDR.(lepr-/lepr-) rats were obese without hyperglycemia. Between 45 and 70 days of age, male but not female obese rats developed T2D. We had previously developed congenic BBDR.(Gimap5-/Gimap5-) rats, which carry an autosomal frameshift mutation in the Gimap5 gene linked to lymphopenia and spontaneous development of type 1 diabetes (T1D) without sex differences. Because the autoimmune-mediated destruction of pancreatic islet beta-cells may be affected not only by obesity but also by the absence of leptin receptor signaling, we next generated BBDR.(lepr-/lepr-,Gimap5-/Gimap5-) double congenic rats carrying the mutation for Gimap5 and T1D as well as the Lepr mutation for obesity and T2D. The hyperleptinemia rescued end-stage islets in BBDR.(lepr-/lepr-,Gimap5-/Gimap5-) congenic rats and induced an increase in islet size in both sexes, while T1D development was delayed and reduced only in females. These results demonstrate that obesity and T2D induced by introgression of the Koletsky leptin receptor mutation in the BBDR rat result in islet expansion associated with protection from T1D in female but not male BBDR.(lepr-/lepr-,Gimap5-/Gimap5-) congenic rats. BBDR.(lepr-/lepr-,Gimap5-/Gimap5-) congenic rats should prove valuable to study interactions between lack of leptin receptor signaling, obesity, and sex-specific T2D and T1D.