scholarly journals Increased weight gain after ovariectomy is not a consequence of leptin resistance

2001 ◽  
Vol 280 (2) ◽  
pp. E315-E322 ◽  
Author(s):  
Yanyun Chen ◽  
Mark L. Heiman

The positive correlation between leptin and body fat mass has caused some investigators to speculate that leptin resistance contributes to obesity. Loss of ovarian function in human and rat is associated with increased fat mass gain and increased circulating leptin levels. To study whether ovariectomy produces leptin resistance, Sprague-Dawley female rats were ovariectomized or sham operated and injected with leptin for 35 days. Ovariectomy (OVX) produced hyperphagia and increased gain in both lean and fat mass. Daily leptin injections initially decreased food intake significantly, but feeding gradually increased to a stable level by day 16and remained at that level for the duration of study. Body composition analysis indicated that chronic injection of leptin to OVX rats dramatically decreased ( P < 0.05) fat mass [30 ± 2 (SE) g, vehicle, to 3 ± 1 g, leptin]. Using indirect calorimetry, we observed that OVX did not change energy expenditure or total level of fuel utilization. Leptin administration increased fat utilization and prevented reduction in calorie expenditure that is typically associated with food restriction. Leptin treatment to OVX rats decreased plasma triglyceride, free fatty acid, and insulin concentrations, whereas glucose concentration was normal. Withdrawal of leptin triggered hyperphagia, indicating that leptin biology remained throughout the duration of the chronic treatment. The same dose of leptin produced qualitatively similar data in sham-operated rats. Thus we concluded that the loss of ovarian function in rats is not associated with a change in leptin sensitivity.

2012 ◽  
Vol 302 (10) ◽  
pp. H2048-H2057 ◽  
Author(s):  
Annie Calvé ◽  
Rami Haddad ◽  
Sarah-Neiel Barama ◽  
Melissa Meilleur ◽  
Igal A. Sebag ◽  
...  

The impact of cancer therapies on adult cardiac function is becoming a concern as more children survive their initial cancer. Cardiovascular disease is now a significant problem to adult survivors of childhood cancer. Specifically, doxorubicin (DOX) may be particularly harmful in young girls. The objective of this study was to characterize DOX damage and determine the ability of dexrazoxane (DEX) to reduce DOX-mediated cardiac damage in sedentary and swim-trained female rats. Female Sprague-Dawley rats were left intact or ovariectomized (OVX) at weaning then injected with DEX (60 mg/kg) before DOX (3 mg/kg), DOX alone, or PBS. Rats were separated into sedentary and swim cohorts. Body weight was reduced in DOX:DEX- but not PBS- or DOX-treated rats. Echocardiographic parameters were similar in sedentary rats. Swim training revealed greater concentric remodeling in DOX-treated rats and reduced fractional shortening in DOX:DEX-treated rats. Calsequestrin 2 was reduced with DOX and increased with DOX:DEX postswim. Sarco(endo)plasmic reticulum Ca2+-ATPase 2a was reduced and calsequestrin 2 reduced further by swim training only in intact rats. OVX rats were heavier and developed eccentric remodeling post-swim with DOX and eccentric hypertrophy with DOX:DEX. Changes in SERCA2a and calsequestrin 2 expression were not observed. Ovariectomized DOX- and DOX:DEX-treated rats stopped growing during swim training. DEX coinjection did not relieve DOX-mediated cardiotoxicity in intact or hormone-deficient rats. DOX-mediated reductions in growth, cardiac function, and expression of calcium homeostasis proteins were exacerbated by swim. DEX coadministration did not substantially relieve DOX-mediated cardiotoxicity in young female rats. Ovarian hormones reduce DOX-induced cardiotoxicity.


2007 ◽  
Vol 293 (3) ◽  
pp. R1056-R1062 ◽  
Author(s):  
Jacqueline Férézou-Viala ◽  
Anne-France Roy ◽  
Colette Sérougne ◽  
Daniel Gripois ◽  
Michel Parquet ◽  
...  

Epidemiological and animal studies suggest that the alteration of hormonal and metabolic environment during fetal and neonatal development can contribute to development of metabolic syndrome in adulthood. In this paper, we investigated the impact of maternal high-fat (HF) diet on hypothalamic leptin sensitivity and body weight gain of offspring. Adult Wistar female rats received a HF or a control normal-fat (C) diet for 6 wk before gestation until the end of the suckling period. After weaning, pups received either C or HF diet during 6 wk. Body weight gain and metabolic and endocrine parameters were measured in the eight groups of rats formed according to a postweaning diet, maternal diet, and gender. To evaluate hypothalamic leptin sensitivity in each group, STAT-3 phosphorylation was measured in response to leptin or saline intraperitoneal bolus. Pups exhibited similar body weights at birth, but at weaning, those born to HF dams weighed significantly less (−12%) than those born to C dams. When given the HF diet, males and females born to HF dams exhibited smaller body weight and feed efficiency than those born to C dams, suggesting increased energy expenditure programmed by the maternal HF diet. Thus, maternal HF feeding could be protective against adverse effects of the HF diet as observed in male offspring of control dams: overweight (+17%) with hyperleptinemia and hyperinsulinemia. Furthermore, offspring of HF dams fed either C or HF diet exhibited an alteration in hypothalamic leptin-dependent STAT-3 phosphorylation. We conclude that maternal high-fat diet programs a hypothalamic leptin resistance in offspring, which, however, fails to increase the body weight gain until adulthood.


Endocrinology ◽  
2007 ◽  
Vol 148 (1) ◽  
pp. 433-440 ◽  
Author(s):  
Christopher D. Morrison ◽  
Christy L. White ◽  
Zhong Wang ◽  
Seung-Yub Lee ◽  
David S. Lawrence ◽  
...  

Animals at advanced ages exhibit a reduction in central leptin sensitivity. However, changes in growth, metabolism, and obesity risk occur much earlier in life, particularly during the transition from youth to middle age. To determine when initial decreases in central leptin sensitivity occur, leptin-dependent suppression of food intake was tested in 8-, 12-, and 20-wk-old male, chow-fed Sprague Dawley rats. Intracerebroventricular leptin injection (3 μg) suppressed 24-h food intake in 8- and 12-wk-old rats (P &lt; 0.05) but not 20-wk-old rats. To identify potential cellular mediators of this resistance, we focused on protein tyrosine phosphatase 1B (PTP1B), a recently described inhibitor of leptin signaling. PTP1B protein levels, as determined by Western blot, were significantly higher in mediobasal hypothalamic punches collected from 20-wk-old rats, compared with 8-wk-old rats (P &lt; 0.05). When 20-wk-old rats were fasted for 24 h, levels of hypothalamic PTP1B decreased (P &lt; 0.05), coincident with a restoration of leptin sensitivity. To directly test whether inhibition of PTP1B restores leptin sensitivity, 20-wk-old chow-fed rats were pretreated with a pharmacological PTP1B inhibitor 1 h before leptin, and 24-h food intake was recorded. As expected, leptin alone produced a small but nonsignificant reduction in food intake. However, pretreatment with the PTP1B inhibitor resulted in a marked improvement in leptin-dependent suppression of food intake (P &lt; 0.05). These data are consistent with the hypothesis that increases in PTP1B contribute to hypothalamic leptin resistance as rats transition into middle age.


2019 ◽  
Vol 149 (3) ◽  
pp. 479-487 ◽  
Author(s):  
Zahra Farahnak ◽  
Julia Lévy-Ndejuru ◽  
Paula Lavery ◽  
Hope A Weiler

ABSTRACT Background Docosahexaenoic acid (DHA; 22:6n–3) is an n–3 (ω-3) fatty acid known for beneficial effects on body composition. Objective The objective of the study was to test the dose response of lean and fat mass to DHA in healthy growing female rats. Methods Female Sprague-Dawley rats (7 wk at baseline; n = 12/diet) were randomly assigned to receive a control (AIN-93M; 60 g soybean oil/kg diet) or experimental diet for 10 wk. Experimental diets contained 0.1%, 0.4%, 0.8%, or 1.2% DHA (wt:wt of total diet). Imaging for whole-body and abdominal composition was conducted using dual-energy X-ray absorptiometry and microcomputed tomography, respectively, at weeks 0, 5, and 10. Fatty acid profiles of several tissues were analyzed using gas chromatography. Serum leptin, C-reactive protein, and plasma insulin-like growth factor I concentrations were measured at each time point using immunoassays. Data were tested using Pearson's correlations and mixed-model ANOVA. Results No differences were observed in weight at baseline or food intake throughout the study. Overall, a 6% increase (P < 0.05) in whole-body and abdominal lean mass was observed in the 0.4%-DHA diet group compared with the control diet group. Moreover, the abdominal visceral fat mass was 31.4% lower in rats in the 0.4%-DHA than in the 1.2%-DHA diet group (P < 0.001). Rats in the 1.2%-DHA diet group showed greater percent differences in whole-body (32.5% and 40.6% higher) and in abdominal (33.9% and 49.4% higher) fat mass relative to the 0.1%- and 0.4%-DHA diet groups, respectively (P < 0.01). Accordingly, serum leptin concentration was lower in the 0.1%-DHA (38.2%) and 0.4%-DHA (43.8%) diet groups (P < 0.01) than in the 1.2%-DHA diet group and positively related to whole-body fat mass (r = 0.91, P < 0.0001). Conclusion Dietary DHA at 0.4% of dietary weight effectively enhances lean mass and proportionally reduces fat mass in growing female rats.


Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2943
Author(s):  
Hui-Hui Xiao ◽  
Xueli Yu ◽  
Chen Yang ◽  
Chi-On Chan ◽  
Lu Lu ◽  
...  

Flavonoids, found in a wide variety of foods and plants, are considered to play an important role in the prevention and treatment of osteoporosis. Our previous studies demonstrated that Erythrina cortex extract (EC) rich in prenylated isoflavonoids exerted bone protective effects in ovariectomized (OVX) rats. The present study aimed to investigate the interactions of gut microbiota with the EC extract to explore the underlying mechanisms involved in its beneficial effects on bone. Sprague-Dawley female rats of 3-months-old were ovariectomized and treated with EC extract for 12 weeks. EC extract reversed ovariectomy-induced deterioration of bone mineral density and bone microarchitecture as well as downregulated cathepsin K (Ctsk) and upregulated runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) in the tibia of OVX rats. Its protective effects on bone were correlated with changes in microbial richness and the restorations of several genera. EC increased the serum circulating levels of acetate and propionate in OVX rats. We conclude that the bone protective effects of EC extract were associated with the changes in microbial compositions and serum short chain fatty acids (SCFAs) in OVX rats.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Andrea Frump ◽  
Amanda Fisher ◽  
Anthony Cucci ◽  
Marjorie Albrecht ◽  
Kara Goss ◽  
...  

Introduction: Women with pulmonary arterial hypertension exhibit more preserved right ventricular (RV) function than men. The underlying mechanisms are unknown. We measured 17beta-estradiol (E2) levels and lung and RV expression of the two main estrogen receptors (ERalpha and -beta) in male and in intact or ovariectomized (OVX) female rats with Su5416/hypoxia (SuHx)-induced pulmonary hypertension (PH). Hypothesis: E2 is required for adaptation to increased RV afterload in females, and ER expression is inversely correlated with PH severity. Methods: Male and age-matched female Sprague-Dawley rats received Su5416 (20mg/kg), followed by 3 weeks of hypoxia (Patm=362 mmHg) and 4 weeks of room air. Selected females underwent OVX with or without concomitant E2 repletion (75 mcg/kg/d). RV hypertrophy (RV/[LV+S]), RV systolic pressure (RVSP), and PA muscularization were measured; complemented by echocardiographic assessment of RV function and measurement of exercise capacity (VO2max). In addition, we assessed RV pro-apoptotic signaling (bcl-2/bax; caspase-3 activity), serum E2 levels, and lung and RV ER expression by Western blot. N was 7-8/group. P<0.05 was considered significant. Results: While no sex differences were noted in RV/(LV+S), RVSP or PA remodeling, female SuHx rats exhibited more preserved cardiac indices (CI; p<0.05). OVX worsened SuHx-induced alterations in RV hypertrophy, RVSP and CI (p<0.05). In turn, E2 replacement in SuHx-OVX rats prevented SuHx-induced alterations in PH endpoints and RV function; this was accompanied by attenuated RV pro-apoptotic signaling. RV ERbeta decreased in OVX SuHx females, but was restored with E2 repletion (p<0.05). RV ERbeta correlated negatively with RVSP and RV/(LV+S), and positively with RV bcl-2/bax (p<0.05). Similarly, serum E2 levels correlated negatively with RVSP and RV/(LV+S) (p<0.05). While healthy females exhibited higher lung ERbeta than healthy males (p<0.05), no such differences were observed in SuHx-PH. Neither lung nor RV ERalpha was affected by PH or hormone depletion. Conclusions: E2 is required for female adaption to SuHx-PH, through a mechanism that may involve ERbeta-mediated RV cell viability signaling, thus allowing for better adaptation to increases in RV afterload.


1995 ◽  
Vol 133 (4) ◽  
pp. 483-488 ◽  
Author(s):  
Andrea C Gallagher ◽  
Timothy J Chambers ◽  
Jonathan H Tobias

Gallagher AC, Chambers TJ, Tobias JH. Distinct effects of ovarian transplantation and exogenous 17 β-oestradiol on cancellous bone of osteopenic ovariectomized rats. Eur J Endocrinol 1995;133:483–8. ISSN 0804–4643 Although 17 β-oestradiol (E2) is known to prevent bone loss, prolonged administration of E2 is unable to reverse this in female rats rendered osteopenic by ovariectomy. To determine whether this reflects a failure to replace other components of ovarian function involved in bone metabolism, we compared the effects of administering E2 to osteopenic ovariectomized (ovx) rats with those of ovarian transplantation. Ovariectomy was performed in female rats. After 13 weeks, by which time marked bone loss had occurred, one group of ovx animals received ovaries from donor rats, and, after a delay of 2 weeks to allow oestrus cycles to return, a further group received E2 5 μg · kg−1 · day−1 for 9 weeks. The dose of E2 was chosen as that which in preliminary studies restored mean serum E2 levels to that of intact female rats. The study was terminated 24 weeks after ovariectomy. Both E2 and ovarian transplantation largely restored indices of oestrogenic exposure in ovx rats to those of sham-ovx animals. Animals receiving ovarian transplants also showed a small increase in serum progesterone and full restoration of serum testosterone. However, while ovarian transplantation also returned indices of cancellous bone metabolism to those of sham-ovx animals, there was little increase in bone volume. Interestingly, exogenous E2 caused a greater increase in cancellous bone volume than ovarian transplantation but also caused more marked suppression of bone formation, as assessed at the end of the study. In conclusion, exogenous E2 and ovarian transplantation exerted distinct effects on skeletal metabolism in osteopenic ovx rats, although the basis for this difference is currently unclear. JH Tobias, Department of Histopathology, St George's Hospital Medical School, London SW17 ORE, UK


2004 ◽  
Vol 97 (4) ◽  
pp. 1237-1244 ◽  
Author(s):  
Mahmoud M. El-Mas ◽  
Abdel A. Abdel-Rahman

We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed α2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with α2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 μg/kg) or α-methyldopa (100 mg/kg), selective I1- and α2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or α-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by α-methyldopa. Ovx significantly enhanced the hypotensive response to α-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced α-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17β-estradiol subcutaneous pellet, 14.2 μg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of α-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates α2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in α-methyldopa-estrogen interaction.


1992 ◽  
Vol 262 (5) ◽  
pp. E557-E560
Author(s):  
C. L. Tsai ◽  
H. F. Pu ◽  
C. P. Lau ◽  
P. S. Wang ◽  
T. K. Liu

The effects of aging on calcitonin (CT) secretion in female rats were investigated. Old (24 mo) at constant diestrus status and young (2 mo) at diestrus status rats were either ovariectomized (Ovx) or left intact as controls. Ovx rats were injected subcutaneously with estradiol benzoate (25 micrograms/kg body wt) or sesame oil one time per day for 3 days. All rats were infused with CaCl2 (10 mg/ml) at a rate of 2 ml/h for 30 min via a jugular catheter connected to a peristaltic pump. Blood samples (0.5 ml each) were collected at 0, 30, 60, and 120 min. The basal and post-CaCl2 levels of plasma Ca measured with radioimmunoassay were significantly higher (P less than 0.05-0.01) in old than in young female rats. The pre- and post-CaCl2 levels of plasma Ca and CT in young rats were not altered by Ovx or estradiol replacement. In old rats, Ovx caused a higher (P less than 0.01) level in plasma CT at 0 and 30 min after CaCl2 infusion. Both basal and stimulated levels of plasma CT were higher (P less than 0.01) in old Ovx than in young Ovx rats. These results demonstrated that 1) the increase of plasma CT in response to Ca challenge was greater in old than in young female rats, 2) the influence of estradiol and ovarian function on plasma CT concentration increases as a function of age, and 3) estradiol reduced the plasma CT in response to hypercalcemia in old Ovx rats. The sensitivity of the target tissue of young rats may be lower in response to the modulation of estrogen during hypercalcemia without compromising the secretion and hypocalcemic effect of CT in young rats. All suggested an age-related relationship between estrogen and CT secretion in minute-to-minute regulation during Ca infusion in rats.


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