scholarly journals Dexamethasone Administration in Mice Leads to Less Body Weight Gain over Time, Lower Serum Glucose, and Higher Insulin Levels Independently of NRF2

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 4
Author(s):  
Fotini Filippopoulou ◽  
George I. Habeos ◽  
Vagelis Rinotas ◽  
Antonia Sophocleous ◽  
Gerasimos P. Sykiotis ◽  
...  

Glucocorticoids are used widely on a long-term basis in autoimmune and inflammatory diseases. Their adverse effects include the development of hyperglycemia and osteoporosis, whose molecular mechanisms have been only partially studied in preclinical models. Both these glucocorticoid-induced pathologies have been shown to be mediated at least in part by oxidative stress. The transcription factor nuclear erythroid factor 2-like 2 (NRF2) is a central regulator of antioxidant and cytoprotective responses. Thus, we hypothesized that NRF2 may play a role in glucocorticoid-induced metabolic disease and osteoporosis. To this end, WT and Nrf2 knockout (Nrf2KO) mice of both genders were treated with 2 mg/kg dexamethasone or vehicle 3 times per week for 13 weeks. Dexamethasone treatment led to less weight gain during the treatment period without affecting food consumption, as well as to lower glucose levels and high insulin levels compared to vehicle-treated mice. Dexamethasone also reduced cortical bone volume and density. All these effects of dexamethasone were similar between male and female mice, as well as between WT and Nrf2KO mice. Hepatic NRF2 signaling and gluconeogenic gene expression were not affected by dexamethasone. A 2-day dexamethasone treatment was also sufficient to increase insulin levels without affecting body weight and glucose levels. Hence, dexamethasone induces hyperinsulinemia, which potentially leads to decreased glucose levels, as well as osteoporosis, both independently of NRF2.

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1045 ◽  
Author(s):  
Atsushi Masuda ◽  
Yusuke Seino ◽  
Masatoshi Murase ◽  
Shihomi Hidaka ◽  
Megumi Shibata ◽  
...  

Long-term exposure to a high starch, low-protein diet (HSTD) induces body weight gain and hyperinsulinemia concomitantly with an increase in β-cell mass (BCM) and pancreatic islets number in mice; however, the effect of short-term exposure to HSTD on BCM and islet number has not been elucidated. In the present study, we investigated changes in body weight, plasma insulin levels, BCM and islet number in mice fed HSTD for 5 weeks followed by normal chow (NC) for 2 weeks. BCM and islet number were increased in mice fed HSTD for 5 weeks compared with those in mice fed NC. On the other hand, mice fed HSTD for 5 weeks followed by NC for 2 weeks (SN) showed decreased BCM and insulin levels, compared to mice fed HSTD for 7 weeks, and no significant differences in these parameters were observed between SN and the control NC at 7 weeks. No significant difference in body weight was observed among HSTD, NC and SN fed groups. These results suggest that a high-starch diet induces an increase in BCM in a manner independent of body weight gain, and that 2 weeks of NC feeding is sufficient for the reversal of the morphological changes induced in islets by HSTD feeding.


1998 ◽  
Vol 274 (6) ◽  
pp. E1057-E1066 ◽  
Author(s):  
Jian Wang ◽  
Jesline T. Alexander ◽  
Ping Zheng ◽  
Hi Joon Yu ◽  
Jordan Dourmashkin ◽  
...  

Patterns of eating behavior, body weight gain, and hormone changes were examined in normal-weight albino Sprague-Dawley rats on macronutrient diets. These diets consisted of either three separate jars with pure macronutrients, fat, carbohydrate and protein, from which to choose, or a single diet with different concentrations of fat and carbohydrate. Similar patterns on the choice-diet and single-diet paradigms were observed. During the first 7–10 days on these diets but not subsequently, the rats consuming a fat-rich diet exhibit significant hyperphagia, an increase in both total and fat intake that produces higher body weight gain. Compared with a 10% fat diet, a 30% fat diet is associated with a decline in insulin and corticosterone (CORT) levels, whereas a 60% fat diet produces an increase in circulating glucose. Levels of glucose are positively correlated with fat intake, and together these measures are consistently related to body fat. These relationships are most strongly expressed in rats that consume a fat-rich diet with >30% fat. Whereas insulin levels are also positively related to body fat, CORT is inversely related in these normal-weight subjects. In animals consuming a high-fat diet, a clear separation can be seen between “obesity-prone” (OP) rats with 100% greater body fat than “obesity-resistant” (OR) rats. The OP rats, which consume 15% more total calories, have significantly higher insulin and glucose levels. In animals that consume a diet with >30% fat, it is the OP but not the OR rats that exhibit a positive relation between fat intake, glucose levels, and body fat and reveal an additional association between carbohydrate intake, insulin, and body fat. Thus these rats on macronutrient diets exhibit distinct traits that relate behavior to hormone disturbances and adiposity and distinguish subjects that are prone vs. resistant to obesity.


2004 ◽  
Vol 92 (5) ◽  
pp. 785-790 ◽  
Author(s):  
M. A. Tormo ◽  
I. Gil-Exojo ◽  
A. Romero de Tejada ◽  
J. E. Campillo

An inhibitor of α-amylase was isolated and purified from an extract of white kidney beans (Phaseolus vulgaris). The acute oral administration of the inhibitor (50 mg/kg body weight) to adult Wistar rats together with a starch load (2 g/kg body weight suspended in NaCl (9 g/l)) reduced the increase in glycaemia over the basal value (NaCl, 222 (SEM 49); inhibitor, 145 (SEM 16) mmol/l×180 min; P<0.05) without modifying the insulin response. On administering the inhibitor orally (50 mg/kg body weight dissolved in NaCl (9 g/l)) for 21 d to rats fed on a standard diet, a decline was observed in the glycaemia values on day 0 (NaCl, 5.53 (SEM 0.12); inhibitor, 5.25 (SEM 0.16) mmol/l) relative to those obtained on days 10 (NaCl, 5.00 (SEM 0.14); inhibitor, 4.60 (SEM 0.08) mmol/l; P<0.05) and 21 (NaCl, 5.22 (SEM 0.22); inhibitor, 4.50 (SEM 0.12) mmol/l; P<0.01) of treatment, without modifying the plasma concentration of insulin. There was found to be a significant anorexigenic action of the inhibitor; there was reduced food intake (NaCl, 23.07 (SEM 0.31); inhibitor, 19.50 (SEM 0.49) g/d; P<0.01), a reduced weight gain (NaCl, 52 (SEM 3); inhibitor, −1.33 (SEM 8.9) g/21 d; P<0.01), as well as changes in the activity of some intestinal enzymes such as maltase (NaCl, 87 (SEM 7); inhibitor, 127 (SEM 11) U/g proteins; P<0.05). The present study has shown, for the first time, that the prolonged administration of an α-amylase inhibitor reduces blood glucose levels and body-weight gain in Wistar rats.


2020 ◽  
Vol 70 (2) ◽  
pp. 144-151
Author(s):  
María del Rocío Padilla Galindo ◽  
Alma Gabriela Martínez Moreno ◽  
Fatima Ezzahra Housni ◽  
Zyanya Reyes Castillo ◽  
Erika Saenz-Pardo Reyes

El consumo de stevia ha sido promovido por su bajo aporte calórico, su efecto antidiabético y antihipercolesterolémico. Sin embargo, los efectos de la ingesta de stevia parecen no ser los mismos para las ratas hembras respecto de los machos. El propósito de este estudio fue evaluar el efecto de la ingesta de stevia sobre el consumo de alimento, peso corporal y niveles de glucosa, insulina, colesterol y triglicéridos en ratas hembras Wistar durante 13 semanas y realizar un análisis predictivo del peso corporal y la ingesta de alimento a 20 semanas. Se utilizaron 20 ratas hembras adultas, que se dividieron en 2 grupos: control (CG) y stevia (SG), ambos grupos recibieron agua y comida a libre acceso, así como una solución de stevia al 0,2 % para el grupo SG. Se registró diariamente el consumo de alimento, agua y solución de stevia; la medición del peso corporal se realizó semanalmente. Al final de las 13 semanas de experimentación, los animales se sacrificaron para evaluar los parámetros metabolicos. El grupo SG mostró un mayor consumo de alimento, mayor proporción de ganancia de peso corporal, niveles de glucosa y colesterol que el grupo CG. No se encontraron diferencias significativas en los niveles de triglicéridos e insulina. Respecto al análisis predictivo (semanas 14-20), se mantiene un incremento significativo en el consumo de alimento y se observa una tendencia de aumento en la proporción de ganancia de peso corporal. Esto indica que el consumo de stevia en ratas hembras parece no tener los mismos efectos benéficos reportados en machos. Consumption of stevia has been promoted due to its low caloric intake, it’s effects as anti-diabetic and anti-hypercholesterolemic. However, the effects of stevia consumption is apparently not the same in females than males. The purpose of this study was to evaluate the effect of stevia intake on meal consumption, body weight and levels of glucose, insulin, cholesterol and triglycerides in female Wistar rats during 13 weeks and develop a predictive analysis of the body weight and meal intake over 20 weeks. 20 adult female rats were utilized, these were divided into two groups: control (CG) and stevia (SG), both groups received free access to water and food, the SG also received a stevia solution at 0.2%. Consumption of food, water and stevia solution was recorded daily, while weight was recorded weekly. At the end of the 13 weeks of experiment, the subjects were sacrificed to evaluate the metabolic parameters. The SG group showed a higher consumption of food, higher proportion of body weight gain, glucose levels and cholesterol than the CG. No significant differences were found in levels of triglyceride or insulin. Respect to the predictive analysis (weeks 14-20), a significant increase in food consumption is maintained and an increasing trend is observed in the proportion of body weight gain. This indicates that stevia consumption appears not to have the same benefit effects in female rats than male rats.


2021 ◽  
Author(s):  
Tanja Jene ◽  
Inigo Ruiz de Azua ◽  
Annika Hasch ◽  
Jennifer Klüpfel ◽  
Julia Deuster ◽  
...  

Stress has a major impact on the modulation of metabolism, as previously evidenced by hyperglycemia following chronic social defeat (CSD) stress in mice. Although CSD-triggered metabolic dysregulation might predispose to pre-diabetic conditions, insulin sensitivity remained intact, and obesity did not develop, when animals were fed with a standard diet (SD). Here, we investigated whether a nutritional challenge, a high fat diet (HFD), aggravates the metabolic phenotype, and whether there are particularly sensitive time windows for the negative consequences of HFD exposure. Chronically stressed male mice and controls (CTRL) were kept under (i) SD-conditions, (ii) with HFD commencing post-CSD, or (iii) provided with HFD lasting throughout, and after CSD. Under SD conditions, stress increased glucose levels early post-CSD. Both HFD regimens increased glucose levels in non-stressed mice, but not in stressed mice. Nonetheless, when HFD was provided after CSD, stressed mice did not differ from controls in long-term body weight gain, fat tissue mass and plasma insulin, and leptin levels. In contrast, when HFD was continuously available, stressed mice displayed reduced body weight gain, lowered plasma levels of insulin, and leptin, and reduced white adipose tissue weights as compared to their HFD-treated non-stressed controls. Interestingly, stress-induced adrenal hyperplasia and hypercortisolemia were observed in mice treated with SD and with HFD after CSD, but not in stressed mice exposed to a continuous HFD treatment. The present work demonstrates that CSD can reduce HFD-induced metabolic dysregulation. Hence, HFD during stress may act beneficially, as comfort food, by decreasing stress-induced metabolic demands.


2020 ◽  
Author(s):  
Yicheng Qi ◽  
Wen Liu ◽  
Xiangsheng Wang ◽  
Wei Liu ◽  
Jing Ma ◽  
...  

Abstract Disease status always affects mesenchymal stem cells (MSCs) function which limits their therapeutical effects. This study aims to evaluate the effects of adipose-derived MSCs (ADSCs) on body weight and glucose homeostasis in obese mice model. After 10 weeks high-fat diet feeding, mice were injected with either phosphate buffered saline (PBS), ADSCs from normal control mice (N-ADSCs) or ADSCs from obese mice (O-ADSCs). Mice fed with chow-fat diet were injected with PBS served as normal controls. Obese mice received O-ADSCs showed slower body weight gain, better blood glucose levels and prevented glucose intolerance deterioration. The inguinal fat weights were reduced in mice receiving O-ADSCs compared to other obese groups, may as the increased lipolysis of inguinal fat. Moreover, O-ADSCs improved insulin signaling molecule expression in muscle. These data reveal that obesity derived autologous ADSCs infusion is an effective treatment for obesity and hyperglycemia.


2008 ◽  
Vol 99 (2) ◽  
pp. 254-261 ◽  
Author(s):  
Judith E. Urías-Silvas ◽  
Patrice D. Cani ◽  
Evelyne Delmée ◽  
Audrey Neyrinck ◽  
Mercedes G. López ◽  
...  

Recent data reported that inulin-type fructans extracted from chicory roots regulate appetite and lipid/glucose metabolism, namely, by promoting glucagon-like peptide-1 (GLP-1) production in the colon. The Agave genus growing in different regions of Mexico also contains important amounts of original fructans, with interesting nutritional and technological properties, but only few data report their physiological effect when added in the diet. Therefore, we decided to evaluate in parallel the effect of supplementation with 10 % agave or chicory fructans on glucose and lipid metabolism in mice. Male C57Bl/6J mice were fed a standard (STD) diet or diet supplemented with Raftilose P95 (RAF), fructans from Agave tequilana Gto. (TEQ) or fructans from Dasylirion spp. (DAS) for 5 weeks. The body weight gain and food intake in mice fed fructans-containing diets were significantly lower than the ones of mice fed the STD diet, TEQ leading to the lowest value. Serum glucose and cholesterol were similarly lower in all fructans-fed groups than in the STD group and correlated to body weight gain. Only RAF led to a significant decrease in serum TAG. As previously shown for RAF, the supplementation with agave fructans (TEQ and DAS) induced a higher concentration of GLP-1 and its precursor, proglucagon mRNA, in the different colonic segments, thus suggesting that fermentable fructans from different botanical origin and chemical structure are able to promote the production of satietogenic/incretin peptides in the lower part of the gut, with promising effects on glucose metabolism, body weight and fat mass development.


1990 ◽  
Vol 68 (2) ◽  
pp. 520-526 ◽  
Author(s):  
C. B. Dolkas ◽  
K. J. Rodnick ◽  
C. E. Mondon

The objectives of this study were to determine how long increased insulin sensitivity, elicited by exercise training, persists after the end of training and what the effect of weight gain is on this retention. Exercise-trained (ET) rats ran voluntarily in freely rotating wheel cages, and insulin sensitivity was assessed by oral glucose tolerance tests (OGTT) and insulin suppression tests (IST). After training, ET rats were retired for 1, 3, or 7 days (R1, R3, or R7). Initial OGTT and IST studies indicated that sensitivity to insulin-induced glucose uptake was increased in ET rats compared with sedentary control (C) rats and was progressively lost with retirement: ET greater than R1 and R3 greater than R7 and C rats, and this reaction was generally associated with a rapid gain in body weight. Subsequent IST tests were performed on C and R7 rats fed laboratory chow or a hypocaloric diet consisting of equal parts of cellulose and chow for 7 days before the test. The results of these tests showed that steady-state serum glucose (SSSG) levels averaged 165 +/- 12 mg/dl for chow-fed C rats and 172 +/- 11 mg/dl for chow-fed R7 rats that gained body weight at rates twice those of C rats. Chow-fed R7 rats, gaining weight at rates comparable to C rats, had SSSG levels of 104 +/- 6 mg/dl. C and R7 rats fed the hypocaloric diet had SSSG values of 102 +/- 6 and 59 +/- 4 mg/dl, respectively. Muscle glycogen levels were comparable in all groups, and liver glycogen was lower in C and R7 rats fed the hypocaloric diet.(ABSTRACT TRUNCATED AT 250 WORDS)


2014 ◽  
Vol 52 (3) ◽  
pp. 235-244 ◽  
Author(s):  
Rihua Zhang ◽  
Dongming Su ◽  
Weidong Zhu ◽  
Qiong Huang ◽  
Menglan Liu ◽  
...  

The aim of this study is to determine the effects of E2 on metabolic syndrome and the molecular mechanisms involving S100A16. Ovariectomized (OVX) rat models and mouse embryonic fibroblasts cell models were used. E2 loss in OVX rats induced body weight gain and central abdominal fat accumulation, which were ameliorated by E2 treatment under chow and high-fat diet (HFD) conditions. E2 decreased the expression of the adipocyte marker genes PPARγ, aP2, C/EBPα, and S100A16. E2 inhibited adipogenesis. Overexpression of S100A16 reversed the E2-induced adipogenesis effect. A luciferase assay showed that E2 inhibited the expression of S100A16. E2 treatment decreased body weight gain and central abdominal fat accumulation under both chow and HFD conditions. Also, E2 suppressed adipogenesis by inhibiting S100A16 expression.


Author(s):  
Amit Goyal ◽  
Anjoo Kamboj

 Objectives: Dopamine plays a critical role in various vital functions, including hormonal regulation, reward, emotions, and food intake. It affects on the multiple aspects of food intake that include food selection, satiety, and energy expenditure. Dopamine D2 receptors (D2R) were found to be lower in several brain regions in both obese experimental animals and humans, and it has been observed that dopamine D2 agonist bromocriptine (BC) can exert favorable metabolic changes in seasonal obesity. The aim of this study was to investigate the beneficial effect of chronic administration of BC a central dopamine receptor agonist on body weight gain, adiposity, and biochemical anomalies in rats.Methods: In this study, chronic administration of BC (2.5 and 5 mg/kg/day, i.p) a dopamine agonist for 8 weeks along with high-fat diet (HFD) to the obese rats which were pretreated with HFD feeding for 8 weeks on the various parameters of obesity were analyzed. The effects of these treatments on body weight, feed intake (kcal), weight and size of fat pads, levels of serum glucose, triglycerides (TG), total cholesterol (TC), high-density lipoproteins (HDL), and low-density lipoprotein were analyzed.Results: Treatment with BC (2.5 and 5 mg/kg/day, i.p) produced significant dose-dependent decrease (p<0.05) in body weight gain, feed intake (kcal), weight and size of fat pads, levels of serum glucose, TG, TC, and low-density lipoproteins as compared to HFD group. Moreover, the level of serum HDL was increased as compared to HFD group. BC a dopamine receptor agonist positively modulate the parameters of obesity, and the effect was comparable to orlistat, a well-reported drug for obesity.Conclusion: In conclusion, the study demonstrates that BC ameliorated established obesity and associated biochemical consequences.


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