Higher Serum Leptin Concentrations Research Articles

Leptin and its relationship with magnesium biomarkers in women with obesity

Some studies have demonstrated the participation of leptin in magnesium metabolism. On the other hand, there is evidence of the role of magnesium in the leptin intracellular signaling pathway. Therefore, the aim of this study was to investigate the existence of a relationship between serum leptin concentrations and magnesium biomarkers in women with obesity. Case-control study involving 108 women aged between 20 and 50years, divided into two groups: obese (n = 52) and control (n = 56). Body weight, height and waist circumference, body mass index, dietary magnesium intake, magnesium biomarkers and serum leptin concentrations were measured. Serum leptin concentrations showed a statistically significant difference between groups (p < 0.001). Mean values of magnesium intake were lower than intake recommended, and with no statistically significant difference between two groups (p > 0.05). Women with obesity had lower plasma and erythrocyte magnesium concentrations than control group did (p < 0.001). Magnesium concentrations found in the urine of women with obesity were higher than the control group was, with a statistically significant difference (p < 0.001). There was a correlation between serum leptin and magnesium biomarkers (p < 0.001). Women with obesity show an inadequate magnesium nutritional status characterized by low plasma and erythrocyte concentrations and high concentrations in urine, and they also have high serum leptin concentrations. Thus, it was possible to observe a correlation between hyperleptinemia and magnesium biomarkers, requiring further studies to determine whether the dysfunction of this hormone can influence the compartmentalization of the mineral in obese organisms.

Abstract 8902: The High Circulating Leptin is Associated With Increased Mortality Risk in Stable Coronary Heart Disease Patients

Introduction: Leptin is an adipocyte-derived peptide, involved in energy homeostasis and regulation of body weight. The position of leptin in cardiovascular pathophysiology remained controversial, some studies suggest a detrimental effect of hyperleptinemia on the cardiovascular (CV) system, while others assume the role of leptin as protective. Hypothesis: We explore whether high leptin status affects the mortality/ morbidity risk in stable patients with coronary heart disease. Methods: 975 patients, ≥6 months after myocardial infarction (EUROASPIRE cohort) were followed in a prospective study. All-cause or CV death, non-fatal events (myocardial infarction, stroke or any revascularization) and hospitalizations for heart failure (HF) were registered as outcomes Results: High serum leptin concentrations (≥18.9 ng/mL, i.e. 4 th quartile) indicate inferior survival, as well as a higher incidence of fatal vascular event or hospitalizations for HF ( see Figure). Even after full adjustment for potential covariates, high leptin was associated with significantly increased 5-years risk of all-cause death [HRR 2.10 (95%CIs:1.29-3.42), p&lt;0.003], CV death [HRR 2.65 (95%CIs:1.48-4.74), p&lt;0.001] and HF hospitalization [HRR 1.95 (95%CIs:1.11-3.44), p&lt;0.020]. In contrast, the incidence risk of non-fatal CV events was only marginally and non-significantly influenced [HRR 1.27 (95%CIs:0.76-2.13), p=0.359] Conclusions: High leptin concentration entails an increased risk of mortality (apparently driven by fatal CV events) and future worsening of HF, on top of conventional CV risk factors and the baseline status of left ventricular function.

The association between leptin concentration and blood coagulation: Results from the NEO study

BackgroundThe adipocyte-derived hormone leptin has been associated with altered blood coagulation in in vitro studies. However, it is unclear whether this association is relevant in vivo and to what extent this association is influenced by total body fat. Therefore, we aimed to examine the association between serum leptin and blood coagulation while taking total body fat into account in a population-based cohort study. MethodsWe performed a cross-sectional analysis with baseline measurements of 5797 participants of the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort of middle-aged men and women. We examined associations between serum leptin concentration and coagulation factor concentrations and parameters of platelet activation in linear regression analyses. All analyses were adjusted for multiple covariates, including total body fat. ResultsIn multivariable adjusted analyses a 1 μg/L higher serum leptin concentration was associated with a 0.22 IU/dL (95% CI: 0.11, 0.32) higher FVIII concentration and a 0.20 IU/dL (95% CI: 0.14, 0.27) higher FIX concentration (3.5 IU/dL FVIII and 3.2 IU/dL FIX per SD leptin). Serum leptin concentration was not associated with FXI, fibrinogen, platelet count, mean platelet volume and platelet distribution width in multivariable adjusted analyses. DiscussionThis study showed that serum leptin concentration was associated with higher concentrations of FVIII and FIX in an observational study, which could be clinically relevant.

Relationship of age at menarche and serum leptin with the metabolically unhealthy phenotype in adolescents.

Objective: to analyze the relationship of age at menarche and leptin with the metabolically healthy (MH) and metabolically unhealthy (MUH) phenotypes in adolescent girls in different body mass index (BMI) categories. Method: an observational and cross-sectional study consisting of 139 female adolescents attended to at the Adolescent Reference Center in Macaé, Rio de Janeiro. Menarche was classified as early (EM) when the first menstruation occurred at or before 11 years of age; normal menarche (NM) was categorized at ages 12 to 14; menarche was considered late (LM) when it occurred at age 15 or older. The factors required to ascertain the subjects' phenotype, as well as their leptin levels, weight, and height, were measured and their BMIs were calculated. The girls were classified as MH or MUH based on the NCEP-ATP III criteria as adapted for children and adolescents. Results: 82 % (n = 114) of the girls were classified as MH and 18 % (n = 25) as MUH. Mean age at menarche was 11.79 ± 1.39 years. There was a higher prevalence of MUH amongst the girls who had EM (p = 0.04). A higher inadequacy of serum leptin concentrations was found in girls who had EM (p = 0.05) and in those classified as MUH (p = 0.01). The adolescents who were severely obese exhibited inadequate leptin levels (p < 0.01) and had gone through EM (p = 0.02). A total of 8.1 % (n = 7) of the normal-weight girls were classified as MUH, and 29.4 % (n = 5) of those who were severely obese were classified as MH (p < 0.01). Conclusion: early menarche and high serum leptin concentrations are related with the MUH phenotype in adolescent girls in different BMI categories.

Dysregulation of Kisspeptin and Leptin, as Anorexigenic Agents, Plays Role in the Development of Obesity in Postmenopausal Women.

During the menopausal period, women have a higher tendency to develop obesity and any other metabolic syndromes. Dysregulation of leptin and kisspeptin signaling as anorexigenic agents is believed to be the connection between metabolic disorders and altered reproductive function. Therefore, this study aimed at investigating the association between leptin, soluble leptin receptor (sOBR), free leptin index, kisspeptin concentrations, and body mass index (BMI) in postmenopausal women. A cross-sectional study was carried out among 171 postmenopausal women aged 40–75 years from 2017 to 2018. Subjects were assigned into 2 groups according to their BMIs: obese group (84 subjects) and nonobese group (87 subjects). In addition to anthropometric measurement, blood sample was collected from each subject for leptin, sOBR, free leptin index (FLI), and kisspeptin evaluation. Bivariate and correlation analysis discovered that leptin and FLI were positively correlated with BMI, while sOBR and kisspeptin were negatively correlated with BMI. Among those variables, multivariate analysis found that leptin, sOBR, and kisspeptin were independently associated with obesity. Therefore, it can be concluded that higher serum leptin concentration and FLI, as well as lower serum sOBR and kisspeptin concentrations, are significantly associated with obesity in postmenopausal women.

Role of adipokines in obstructive airway disease and diabetes mellitus

This review summarizes the state of the current literature relating to the associations of lung disease and adipokines (proteins produced by adipose tissue) in humans. The mechanistic basis for these associations in humans is not established, although a possible role for adipokines has been invoked. Leptin, a pro-inflammatory adipokine, and adiponectin, an anti-inflammatory adipokine, are causally associated with asthma in mice. Although human studies are currently inconclusive, high-serum leptin and low-serum adiponectin concentrations predict asthma, independent of obesity, in select population groups, such as premenopausal women in the United States. In contradistinction, low-serum leptin and high-serum adiponectin concentrations are associated with stable COPD, although these associations are likely confounded by fat mass. Interestingly, leptin may promote systemic and airway inflammation in stable COPD patients. On the other hand, COPD may upregulate systemic and lung adiponectin expression. The precise mechanism and significance of the associations between these adipokines and lung disease at the current stage are confusing and frankly paradoxical in places. It is now known that adipose tissue is not an inert organ simply for energy storage, but regulates systemic inflammation via a variety of secreted proteins (called adipokines). While the associations of obesity and adipokines with cardiovascular, endocrine, and rheumatological diseases are well described, the respiratory effects of obesity and adipokines are less well known. This review will focus on the effect of obesity and adipokines on asthma and chronic obstructive pulmonary disease (COPD) in humans. This area of research needs additional study that may open up novel therapeutic strategies for these lung diseases.

Role of adipokines in obstructive airway disease and diabetes mellitus

This review summarizes the state of the current literature relating to the associations of lung disease and adipokines (proteins produced by adipose tissue) in humans. The mechanistic basis for these associations in humans is not established, although a possible role for adipokines has been invoked. Leptin, a pro-inflammatory adipokine, and adiponectin, an anti-inflammatory adipokine, are causally associated with asthma in mice. Although human studies are currently inconclusive, high-serum leptin and low-serum adiponectin concentrations predict asthma, independent of obesity, in select population groups, such as premenopausal women in the United States. In contradistinction, low-serum leptin and high-serum adiponectin concentrations are associated with stable COPD, although these associations are likely confounded by fat mass. Interestingly, leptin may promote systemic and airway inflammation in stable COPD patients. On the other hand, COPD may upregulate systemic and lung adiponectin expression. The precise mechanism and significance of the associations between these adipokines and lung disease at the current stage are confusing and frankly paradoxical in places. It is now known that adipose tissue is not an inert organ simply for energy storage, but regulates systemic inflammation via a variety of secreted proteins (called adipokines). While the associations of obesity and adipokines with cardiovascular, endocrine, and rheumatological diseases are well described, the respiratory effects of obesity and adipokines are less well known. This review will focus on the effect of obesity and adipokines on asthma and chronic obstructive pulmonary disease (COPD) in humans. This area of research needs additional study that may open up novel therapeutic strategies for these lung diseases.

Leptin induces osteoblast differentiation of human valvular interstitial cells via the Akt and ERK pathways.

Calcific aortic valve disease (CAVD) affects 2-6% of the population over 65years, and age, gender, smoking, overweight, dyslipidemia, diabetes contribute to the development of this disease. CAVD results, in part, from the osteoblast differentiation of human valvular interstitial cells (VICs). This study aims to elucidate the effects of leptin on osteoblast phenotype of VICs and the signalling pathways involved. Patients who underwent aortic valve replacement for CAVD (n=43) were included in this study. Patients with coronary artery disease (CAD) without CAVD (n=129) were used as controls. Patients with CAVD had higher serum leptin concentrations than CAD patients (p=0.002). Leptin was found in calcific aortic valves, with higher concentrations in calcified versus non-calcified zones (p=0.01). Chronic leptin stimulation of human VICs enhanced alkaline phosphatase (ALP) activity and ALP, BMP-2 and RUNX2 expression and decreased osteopontin expression. Moreover, inhibiting Akt or ERK during leptin stimulation lowered the expression of osteoblast markers in VIC. Taken together, these findings indicate that leptin plays a critical role in CAVD development by promoting osteoblast differentiation of human aortic VICs in an Akt- and ERK-dependent manner. This study highlights the role of leptin in CAVD development, and further studies are needed to determine whether reducing circulating leptin levels or blocking leptin actions on VICs is efficient to slow CAVD progression.

Leptin and its potential interest in assisted reproduction cycles.

Leptin, an adipose hormone, has been shown to control energy homeostasis and food intake, and exert many actions on female reproductive function. Consequently, this adipokine is a pivotal factor in studies conducted on animal models and humans to decipher the mechanisms behind the infertility often observed in obese women. A systematic PubMed search was conducted on all articles, published up to January 2015 and related to leptin and its actions on energy balance and reproduction, using the following key words: leptin, reproduction, infertility, IVF and controlled ovarian stimulation. The available literature was reviewed in order to provide an overview of the current knowledge on the physiological roles of leptin, its involvement in female reproductive function and its potential interest as a prognostic marker in IVF cycles. Animal and human studies show that leptin communicates nutritional status to the central nervous system and emerging evidence has demonstrated that leptin is involved in the control of reproductive functions by acting both directly on the ovaries and indirectly on the central nervous system. With respect to the clinical use of leptin as a biomarker in IVF cycles, a systematic review of the literature suggested its potential interest as a predictor of IVF outcome, as high serum and/or follicular fluid leptin concentrations have correlated negatively with cycle outcome. However, these preliminary results remain to be confirmed. Leptin regulates energy balance and female reproductive function, mainly through its action on hypothalamic-pituitary-ovarian function, whose molecular and cellular aspects are progressively being deciphered. Preliminary studies evaluating leptin as a biomarker in human IVF seem promising but need further confirmation.

Abstract 15192: Leptin Effects on Osteoblast Differentiation of Human Valvular Interstitial Cells: New Insight Into Calcific Aortic Valve Disease

Introduction: Calcific aortic valve disease (CAVD) affects 2% to 6% of the population over 65 years and results from dysregulated processes such as calcification, supported in part by the osteoblast differentiation of valvular interstitial cells (VIC), the most prevalent cell type in the human aortic valves. Leptin has recently been linked to aortic valve calcification in ApoE-/- mice. Hypothesis: Our hypothesis is that leptin could play a role in the calcifying processes implicated in CAVD via direct effects on human VIC. Methods: Patients who underwent aortic valve replacement for severe CAVD (n=43) or with coronary artery disease (CAD) but without CAVD (n=129) were included in this study. Presence of leptin was analyzed in human explanted calcified aortic valves and blood samples. Leptin receptors expression was analyzed in aortic valves and VIC isolated from aortic valves. Leptin effects on osteoblast differentiation of VIC in presence or not of Akt and ERK inhibitors were investigated by alizarin red staining, alkaline phosphatase (ALP) activity, and RT-qPCR analysis for osteopontin, ALP, bone morphogenetic protein BMP-2, and RUNX2. Results: Patients with CAVD have significant higher serum leptin concentration than CAD patients (p=0.002). The presence of leptin was observed by immunochemistry in human calcified aortic valves, with higher concentrations in calcified vs non-calcified zones (p=0.01). Both short and long leptin receptor isoforms were expressed in VIC. Chronic leptin stimulation of VIC enhanced ALP, BMP-2 and RUNX2 expression and decreased osteopontin expression. This treatment led to a higher, dose dependent, ALP activity and calcium deposition in VIC. Inhibiting Akt or ERK during leptin stimulation led to a reduced calcification by bringing the expression of calcification genes to the control levels. Conclusions: Together, these novel findings depict the potential role of leptin in the process of CAVD by triggering calcification processes in human VIC.

Leptin Inhibits the Apoptosis of Endometrial Carcinoma Cells Through Activation of the Nuclear Factor κB–inducing Kinase/IκB Kinase Pathway

Leptin has recently been shown to affect cancer proliferation and invasion through multiple pathways. In the current study, we investigated the role of leptin in endometrial carcinoma (EC) apoptosis and the underlying mechanisms of action. Immunoprecipitation was used to characterize leptin receptor expression in EC lines. The levels of nuclear factor κB-inducing kinase (NIK)/IκB kinase (IKK) signaling proteins were analyzed using Western blot. In addition, Western blot and immunohistochemical analyses were used to detect the hierarchy of these proteins in EC tissues. Quantitative cancer cell apoptosis assay was performed using flow cytometry after incubation of cells with Annexin-V/fluorescein/propidium iodide, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide or staining of cancer cell DNA fragments with propidium iodide. Leptin induced a decrease in apoptosis in Ishikawa and HEC-1A EC cells, partly through nuclear factor κB activation via phosphorylation in the IKK/NIK pathway. Inhibition of IKK or NIK partly neutralized this suppression of apoptosis. Expression levels of leptin receptors (Ob-Rs) and IKK/NIK signaling proteins were higher in poorly and moderately differentiated than in well-differentiated EC tissues, and higher Ob-Rs expression was observed in clinical stages II and III, compared with stage I EC (P = 0.012). High serum leptin concentration displayed mild correlation (r = 0.23, P = 0.035) with degree of EC differentiation. Leptin inhibits EC apoptosis partly through activation of the NIK/IKK pathway in vitro. Ob-Rb overexpression seems to facilitate EC progression.

Maternal dietary protein supplement confers long-term sex-specific beneficial consequences of obesity resistance and glucose tolerance to the offspring in Brandt's voles

Maternal under- or over-nutrition not only alters neonatal body mass but also increases the risk of metabolic disorders in adulthood. Little is known about how maternal dietary protein affects offspring fitness in wild rodents. The present study was conducted to test the hypothesis that maternal dietary protein supplement has a long-term beneficial effect on offspring fitness in Brandt's vole (Lasiopodomys brandtii), a herbivorous rodent model. The vole dams were fed either a control (18% protein) or high-protein (36% protein) diet throughout pregnancy and lactation. After weaning, all offspring received a control diet till 14weeks old. Energetic parameters, serum leptin concentration and glucose tolerance were measured. The adult offspring were fed high-fat diet for 8weeks, and body weight and food intake were measured. No difference was observed in litter size, litter mass or pup mass before weaning. Maternal protein supplement increased body mass and the mass of reproductive organ but decreased digestibility and fat deposition and alleviated HFD-induced obesity especially in the males. Glucose tolerance was elevated in the offspring from maternal protein supplement, especially in the females. The accelerated growth may be associated with high serum leptin concentration at weaning, a state of leptin resistance, and the low digestibility may predispose obesity resistance especially in male offspring from maternal high-protein diet. These data demonstrate that maternal protein supplement confers the long-term sex-specific beneficial consequences of accelerated growth and improved obesity resistance and glucose tolerance of their offspring.

High Bone Density in Adolescents With Obesity Is Related to Fat Mass and Serum Leptin Concentrations

Obesity has been associated with increased bone mass, but the mechanisms involved are still poorly understood. We aimed to explore the relation between bone mineral density and factors known to influence bone formation in obese and lean adolescents. We recruited 24 obese and 25 lean adolescents in a case-control study. Total body bone mineral density (TB-BMD) z scores and body composition were determined using dual-energy x-ray absorptiometry. We measured 25-hydroxyvitamin D (25-OH-D), glucose, insulin, and leptin concentrations. Physical activity (PA) level was quantified using accelerometer. TB-BMD z score was higher, whereas 25-OH-D and PA levels were lower in obese compared with lean subjects (TB-BMD z score 1.06 ± 0.96 vs 0.26 ± 0.91, P = 0.004; 25-OH-D 9.9 ± 6.4 vs 18.5 ± 7.4 ng mL, P < 0.001; PA level 308.3 ± 22.1 vs 406.8 ± 29.2 count min, P = 0.01). TB-BMD z score was not related to 25-OH-D or PA levels, but was positively correlated with leptin concentration and fat mass (P < 0.05). Vitamin D concentration was negatively correlated with fat mass (P < 0.001). Despite lower serum vitamin D and PA levels, BMD was higher in adolescents with obesity and associated with higher serum leptin concentrations. Furthermore, adolescents with obesity have lower vitamin D serum concentrations than lean controls, probably owing to its distribution in adipose tissue.

Appetite loss may be induced by lower serum ghrelin and higher serum leptin concentrations in subarachnoid hemorrhage patients

BackgroundPatients with aneurysmal subarachnoid hemorrhage (SAH) typically develop appetite loss. However, the mechanisms regulating appetite are not understood. Ghrelin and leptin, both of which signal nutritional status and energy storage levels to the hypothalamus, are essential elements of the appetite system. Thus, the goal of this study was to investigate the relationship between appetite and ghrelin and leptin concentrations in patients with SAH.MethodsBlood plasma or serum profiles and appetite status were measured in 19 patients with SAH who underwent aneurysmal clipping within 48 hours of SAH onset. Appetite status was measured using dietary oral calorie intake. All outcome variables were measured at an early (day 3) and late (day 8) time point after SAH onset (day 0).ResultsOf the 19 patients studied, 6 (31.6%) showed lower dietary oral calorie intake at the late time point than at the early time point. In these patients with appetite loss, plasma hemoglobin (P < 0.02), albumin (P < 0.01), glucose (P < 0.01), plasma insulin (P < 0.04), and serum ghrelin (P < 0.03) concentrations were lower at the late time point than at the early time point. Serum leptin was higher at the late time point than at the early time point (P < 0.02).ConclusionIn SAH patients, appetite loss may be induced by lower serum ghrelin and higher serum leptin concentrations resulting from high plasma glucose and insulin levels due to a catecholamine surge following SAH.

SAT0318 Association between joint pain severity and serum leptin levels in hand osteoarthritis

BackgroundA possible link between obesity, adipocytokines (leptin) and pain severity in osteoarthritis (OA) has been suggested. Synovial leptin levels are increased in OA, particularly in women and in obese patients....

Serum leptin, adiponectin and endometrial cancer risk in Chinese women

ObjectiveTo investigate the relationship between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women.MethodsWe conducted a case-control study of a total of 516 Chinese women to detect the relationships between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women. The study subject constituted 206 cases of endometrial cancer and 310 normal controls.ResultsPatients with endometrial carcinoma had higher serum leptin concentrations than controls (28.8±2.2 ug/L vs. 19.8±1.4 ug/L; p<0.001). The adiponectin levels in patients were lower than in controls with borderline statistical significance (2,330.7±180.5 ug/L vs. 2,583.9±147.2 ug/L; p=0.078). Logistic regression analysis confirmed the associations between leptin or adiponectin, and endometrial carcinoma after adjustment for age, body mass index, fasting insulin, serum glucose, cholesterol, triglycerides, and high-density lipoprotein cholesterol (odds ratio for the top tertile vs. the bottom tertile: leptin 2.05; 95% confidence interval [CI], 1.28 to 3.29; p<0.001; adiponectin 0.52; 95% CI, 0.32 to 0.83; p<0.001).ConclusionIncreased leptin or decreased adiponectin levels are associated with endometrial carcinoma.

Serum leptin and ghrelin concentrations in chronic hepatitis C genotype-4 patients with steatosis: their effect on the response to antiviral therapy

BackgroundThe precise pathogenic mechanisms of steatosis among patients with chronic hepatitis C (CHC) still remain largely unknown. Recent evidences identified various adipokines and gut hormones as relevant modulators of the pathophysiology of liver fibrosis and steatosis progression. We assessed whether pretreatment serum leptin and ghrelin concentrations differ in steatotic patients infected with hepatitis C virus (HCV) genotype-4 and whether these concentrations are associated with response to antiviral treatment.Participants and methodsThis study was conducted on 50 patients with CHC genotype-4 and steatosis and 25 age-matched healthy participants as a control group. Patients were treated with Peg-interferon and ribavirin for 48 weeks, independent of virologic response. Serum HCV-RNA concentrations were measured before the initiation of treatment and at weeks 12, 24, and 48 during the treatment. The genotype was determined using INNO-LIPA HCV assays, and serum leptin and ghrelin concentrations were measured using enzyme-linked immunosorbent assay. Biopsy specimens were scored according to the Ishak system, and steatosis was graded as mild, moderate, or severe.ResultsWe found high insulin resistance and serum leptin concentrations and low plasma ghrelin concentrations at baseline in patients with CHC compared with the healthy controls (P = 0.000). Serum leptin levels tend to increase (P = 0.023), whereas plasma ghrelin levels tend to decrease (P = 0.004) as the grade of steatosis worsens. Plasma ghrelin at baseline showed significant negative correlations with insulin resistance and leptin. However, we did not find any correlations between leptin, ghrelin, insulin resistance, hepatic fibrosis, and hepatic steatosis with viral load. Sustained virological response (SVR) was achieved in 28 patients (56%) and was associated with a lower grade of liver steatosis (P = 0.013), milder fibrosis (P = 0.002), low value of insulin resistance (P = 0.001), lower leptin levels (P = 0.005), and higher ghrelin levels (P = 0.001), whereas patients who did not achieve SVR (nonresponder) had significantly higher leptin and lower ghrelin concentrations at baseline, with significant difference as the severity of steatosis worsened.ConclusionIncreased serum leptin before treatment may predict non-SVR, whereas increased ghrelin may predict SVR. Ghrelin exerts antifibrotic effects on the liver and may represent a novel antifibrotic therapy.

Effects of sex and scotorefractory state on obesity induced by photostimulation and serum leptin in Siberian hamsters (Phodopus sungorus)

The rising prevalence of obesity is associated with an increasing incidence of heart disease, diabetes and other health risks. In addition, severe cases of obesity are associated with an even greater risk of morbidity and mortality. Therefore, animal models of morbid obesity are required to better elucidate the underlying mechanisms. Our investigations in the Siberian hamster (Phodopus sungorus) suggest that pronounced obesity can be reliably induced in this species without relying on genetic manipulation or overly fatty and palatable foods. In a prior study on reproductive aging in female Siberian hamsters, we incidentally observed marked obesity in a group of hamsters that were exposed to a particular photoperiodic regime. In short day (SD) lengths, Siberian hamsters inhibit their reproductive physiology and reduce food intake and body mass. However, hamsters become refractory to SD after 15–20weeks and revert to the long day (LD) phenotype. In the previous study, refractory animals appeared to be particularly sensitive to photostimulation (transfer to LD), in terms of increasing body mass. To test the hypothesis that refractoriness to SD predisposes hamsters to severe obesity, we photostimulated females and males in different states of SD responsiveness (inhibited or refractory). We determined that photostimulation during the SD-refractory state is particularly effective in inducing pronounced obesity and high serum leptin concentration in female hamsters. We propose that this experimental framework is a useful model to investigate the factors and signals that create a predisposition to excessive food intake and body mass, without having to rely on genetic or dietary manipulations.

Physical training prevents body weight gain but does not modify adipose tissue gene expression

The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P < 0.05). S mice had a substantial weight gain compared to T mice (4.06 ± 0.43 vs 0.38 ± 0.28 g, P < 0.01). WAT mass, adipocyte size, and the weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05). Food intake was higher in T than S mice (4.7 ± 0.2 vs 4.0 ± 0.3 g/animal, P < 0.05) but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 ± 0.5 vs 3.11 ± 0.12 ng/mL). WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns.

Effect of immune stress on body weight regulation is altered by ovariectomy in female rats

It has been suggested that obesity and loss of ovarian function alter the inflammatory response to immune stress. Ovariectomized (OVX) rats, which are used as a model of human menopause, exhibit both hyperphagia-induced obesity and gonadal steroid deficiency. To evaluate the effects of ovariectomy on inflammatory responses, we compared the anorectic response to LPS in OVX rats and gonad intact female rats. As leptin and hypothalamic interleukin-1β (IL1β) play pivotal roles in the anorectic response to immune stress, these factors were also measured. It was found that the OVX rats exhibited an increased anorectic response to LPS compared with the sham-operated rats. The OVX rats showed higher serum leptin concentrations and a greater increase in hypothalamic IL1β mRNA expression after LPS injection. In addition, in order to determine whether gonadal steroid deficiency contributes to the changes in the inflammatory responses of OVX rats, we compared responses between OVX rats treated with gonadal steroids and untreated OVX rats. There were no differences in appetite, the serum leptin level, and hypothalamic IL1β mRNA expression between the two groups after LPS injection. These findings suggest that the loss of ovarian function increases the induction of leptin and hypothalamic IL1β synthesis and consequently increases the anorectic response under immune stress conditions. It is possible that these alterations are caused by OVX-induced obesity rather than the direct effects of gonadal steroid deficiency.