scholarly journals Reduced body weight at weaning followed by increased post-weaning growth rate interacts with part-per-trillion fetal serum concentrations of bisphenol A (BPA) to impair glucose tolerance in male mice

PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0208846 ◽  
Author(s):  
Julia A. Taylor ◽  
Jennifer M. Sommerfeld-Sager ◽  
Chun-Xia Meng ◽  
Susan C. Nagel ◽  
Toshi Shioda ◽  
...  
2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jihye Lee ◽  
Seong-Ho Lee

Abstract Objectives Patchouli alcohol is a sesquiterpene alcohol found in Pogostemon cablin. Recently, we observed that patchouli alcohol reduced lipid accumulation in differentiated 3T3-L1 adipocytes and increased glucose uptake in differentiated C2C12 myocytes. This study was designed to investigate anti-obese and anti-diabetic activities of patchouli alcohol using high fat diet-induced obese mouse model. Methods Forty-eight 5-week old C57BL/6 J male mice were assigned into four groups and fed with 1) normal diet (control), 2) high fat diet, 3) high fat diet with gavaging 25 mg of patchouli alcohol/kg body weight and 4) high fat diet with gavaging 50 mg of patchouli alcohol/kg body weight. High fat diet or control diets were provided to each treatment group for four weeks and then different doses of patchouli alcohol (0, 25 or 50 mg/kg body weight) was orally administered for following 8 weeks with the diet. At age of week 17, all animals were sacrificed, fat tissues were collected, and tissue weight was measured. In addition, twenty C57BL/6 J male mice were assigned into the same treatment groups above. At the end of the 8 weeks (age of week 17), the mice were fasted for 12 h and the oral glucose tolerance test was performed after intraperitoneal injection of 2 g of anhydrous glucose/kg body weight. The blood was collected from tail at 0, 15, 30, 90 and 120 min after injection and blood glucose level was analyzed using glucose meter. Results Treatment of patchouli alcohol (50 mg/kg body weight) significantly reduced body weight and accumulation of body fat pads which was highly induced by feeding of high fat diet. An analysis of individual fat pad weights (expressed as mg weight of fat pad/g body weight) revealed a significant decrease of epididymal and retroperitoneal fat pad in patchouli alcohol-treated mice whereas brown adipose tissue were not significantly altered. And, slightly improved glucose tolerance was observed at 90 and 120 minutes after glucose injection in mice treated with patchouli alcohol (50 mg/kg body weight) compared to those fed with high fat diet alone. Conclusions We propose a potential use of patchouli alcohol as an anti-obesity compound in obese population. Funding Sources NIFA Hatch grant. Supporting Tables, Images and/or Graphs


2015 ◽  
Vol 226 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Min Kyong Moon ◽  
In-Kyong Jeong ◽  
Tae Jung Oh ◽  
Hwa Young Ahn ◽  
Hwan Hee Kim ◽  
...  

Bisphenol A (BPA) is a widely used endocrine disruptor. Recent epidemiologic results have suggested an association between exposure to BPA and cardiovascular disease, type 2 diabetes, and obesity. We investigated the in vivo effects of long-term oral exposure to BPA on insulin resistance and glucose intolerance. In the present study, 4- to 6-week-old male mice on a high-fat diet (HFD) were treated with 50 μg/kg body weight per day of BPA orally for 12 weeks. Long-term oral exposure to BPA along with an HFD for 12 weeks induced glucose intolerance in growing male mice. Intraperitoneal glucose tolerance tests showed that the mice that received an HFD and BPA exhibited a significantly larger area under the curve than did those that received an HFD only (119.9±16.8 vs 97.9±18.2 mM/min, P=0.027). Body weight, percentage of white adipose tissue, and percentage of body fat did not differ between the two groups of mice. However, treatment with BPA reduced Akt phosphorylation at position Thr308 and GSK3β phosphorylation at position Ser9 in skeletal muscle. BPA tended to decrease serum adiponectin levels and to increase serum interleukin 6 and tumor necrosis factor α, although these findings were not statistically significant. Treatment with BPA did not induce any detrimental changes in the islet area or morphology or the insulin content of β cells. In conclusion, long-term oral exposure to BPA induced glucose intolerance and insulin resistance in growing mice. Decreased Akt phosphorylation in skeletal muscle by way of altered serum adipocytokine levels might be one mechanism by which BPA induces glucose intolerance.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2421-2421
Author(s):  
Constance Tom Noguchi ◽  
Heather Marie Rogers

Erythropoietin (EPO) promotes erythroid differentiation and increases glucose uptake in erythroid progenitor cells in culture. The metabolic burden associated with EPO treatment in adult mice is suggested by a decrease in body weight concomitant with increased hematocrit. Wild type male mice (C57Bl/6, age 8 months) treated with EPO showed the expected increase in hematocrit accompanied by a fall in blood glucose level and a decrease in body weight and fat mass. However, the decrease in body weight is even more evident in obese mice on a high fat diet and has also been linked to non-hematopoietic response, particularly with EPO receptor (EpoR) expression in white adipose tissue. We examined the metabolic burden of EPO treatment (3000U/kg for 3 weeks) in young, lean male mice (3 months) placed on high fat diet at the time of EPO administration. The increase in hematocrit was accompanied by decreased blood glucose level and improved glucose tolerance. However, no difference in body weight was observed between mice treated with EPO and the saline treated group, suggesting that the EPO stimulated decrease in body weight is evident primarily in older animals with greater fat mass. To determine the contribution of EpoR expression in non-hematopoietic tissue to the metabolic EPO response, young male mice with EpoR restricted to erythroid tissue (TgEpoR) were placed on high fat diet and treated with EPO. The expected increased hematocrit was also accompanied by decreased blood glucose level and improved glucose tolerance, and no change in body weight between EPO and saline treatment. The similar responses observed in young wild type and TgEpoR mice suggest that the EPO stimulated increase in glucose metabolism is associated with increased erythropoiesis rather than a direct EPO response in non-hematopoietic tissue. TgEpoR mice exhibit an age dependent increase in fat mass even greater than that observed in wild type mice, and by 8 months TgEpoR mice are obese, glucose intolerant and insulin resistant compared with wild type mice. At 8 months, TgEpoR mice treated with EPO show the increase in hematocrit and, despite the increase in fat mass, there is only a minimal decrease in body weight compared with wild type mice. These data provide evidence that in addition to the age dependent association of EPO stimulated decrease in body weight and fat mass, this decrease in body weight is due largely to EPO response related to EpoR expression in non-hematopoietic tissue. Interestingly, young male mice with targeted deletion of EpoR in adipose tissue placed on a high fat diet and treated with EPO show the increase in hematocrit and improvement in glucose tolerance, and at 8 months, the increase in hematocrit with EPO treatment is accompanied by minimal change in body weight. The similar metabolic response of these mice with targeted deletion of EpoR in adipose tissue to TgEpoR mice indicate the contribution of EpoR expression in adipose tissue to the loss of body weight and fat mass. Therefore, the metabolic burden associated with EPO stimulated erythropoiesis appears to be reflected in improved glucose metabolism and glucose tolerance with minimal or no effect on body weight, is evident in young, lean mice, and is independent of EpoR expression in non-hematopoietic tissue. In older mice, non-hematopoietic metabolic EPO response is more readily apparent as reflected in loss of body weight/fat mass, which overshadows the erythropoietic metabolic response. In combination, the metabolic response to EPO treatment results from EPO stimulated increased erythropoiesis, improved glucose metabolism and glucose tolerance, and an age dependent decrease in body weight and fat mass associated with EpoR expression in non-hematopoietic tissue, particularly in white adipose tissue. Disclosures No relevant conflicts of interest to declare.


2013 ◽  
Vol 82 (2) ◽  
pp. 147-151 ◽  
Author(s):  
Stanisław Milewski ◽  
Roman Wójcik ◽  
Bożena Zaleska ◽  
Joanna Małaczewska ◽  
Zenon Tański ◽  
...  

The aim of this study was to determine the effect of Saccharomyces cerevisiae on indicators of meat performance traits in sheep as well as on selected non-specific indicators of humoral and cellular defense. The experiment was performed on 32 suckling Kamieniec lambs divided into two equal groups (control and experimental). Over a period of 60 days, experimental group of lambs were fed a diet supplemented with Saccharomyces cerevisiae dried yeast (the yeast supplement did not change the value of the feed ration). The following meat performance indicators were determined: body weight, daily gains, growth rate, the dimensions of musculus longissimus dorsi sections, skin and subcutaneous fat thickness and fat thickness over the loin “eye” area. Selected indicators of non-specific humoral immunity (lysozyme activity, ceruloplasmin activity, total protein and gamma globulin content) were determined in the blood serum of lambs. Compared to control, yeast administered to the experimental group of lambs significantly increased the values of the analyzed meat performance traits i.e. body weight, growth rate, musculus longissimus dorsi dimensions (P ≤ 0.05) and daily gains (P ≤ 0.01), pointing to improved muscle development. Lambs fed the yeast showed a significant (P ≤ 0.01) increase in lysozyme and ceruloplasmin activity and increased serum concentrations of gamma globulins. Significant differences between the experimental and control groups were not observed only with respect to the serum concentrations of total protein. Suuplementing the lambs’ feed with yeast had a positive effect on meat performance traits and indicators of humoral immunity.


Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3690-3699 ◽  
Author(s):  
Nicole Wong ◽  
Barbara C. Fam ◽  
Gitta R. Cempako ◽  
Gregory R. Steinberg ◽  
Ken Walder ◽  
...  

Obesity is a chronic low-grade inflammatory disease caused by increased energy intake and reduced energy expenditure. Studies using animal models with deletion of inflammatory cytokines have produced conflicting results with some showing increased weight gain and others showing no effect or even reduced body weights. Clearly, more work is necessary to understand the role of cytokines on body weight control. The aim of this study was to determine the effect of interferon-γ deletion (IFNγ−/−) on body weight regulation and glucose metabolism. Male IFNγ−/− and wild-type C57BL/6 mice were fed a low-fat chow diet, and body weight, food intake, and energy expenditure were monitored over 20 wk. At the end of the study, ip glucose tolerance test, insulin tolerance test, basal glucose turnover, and hyperinsulinemic/euglycemic clamps were performed. Expression levels of arcuate nucleus neuropeptide Y, Agouti-related peptide, and proopiomelanocortin mRNA as well as circulating leptin levels were also determined. IFNγ−/− mice had improved glucose tolerance with reduced rate of glucose appearance and increased insulin sensitivity due to greater suppression of endogenous glucose output, which was associated with decreased hepatic glucose-6-phosphatase activity. In addition, we also observed reduced body weight associated with decreased food intake and increased physical activity. Neuropeptide Y and Agouti-related peptide mRNA expression was reduced, whereas proopiomelanocortin mRNA expression was increased, as were plasma leptin levels. Global deletion of IFNγ in mice resulted in reduced body weight associated with negative energy balance, improved glucose tolerance, and hepatic insulin sensitivity. Our findings demonstrate that IFNγ plays a critical role in the regulation of body weight and glucose metabolism.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Luane da Guia Vieira ◽  
Alan Carlos Fernandes ◽  
Tais Nascimento ◽  
Suzelei de Castro França ◽  
Jose Antunes-Rodrigues ◽  
...  

Abstract POMC neurons expressed in the ARC are essential for energy balance and glucose homeostasis. It has been suggested the involvement of these neurons in the control of endocrine axes, such as the HPA. During fasting, POMCARC neurons are silenced as an effort to reduce body weight loss and to avoid hypoglycemia. During this process glucocorticoid secretion and activation of enzymes involved in the hepatic gluconeogenesis take place in order to preserve the homeostasis. In this study, to clarify the contribution of POMCARC neurons to the adaptive changes in energy homeostasis, glucose metabolism and HPA axis activity induced by food deprivation we used DREADDs to specifically activate POMCARC. Bilateral injections of the AAV carrying the excitatory DREADD (hM3DGq) or only the reporter gene (mCherry) have been performed into the ARC of Pomc-ires-cre and WT mice. Two weeks later the animals were fasted for 36hr, treated with saline (5 i.p. injections each 8hrs) and blood samples were collected from the facial vein at 10am. Two weeks apart, the same animals were submitted to another period of fasting and treated with CNO (1mg/Kg, 5 i.p. injections each 8hrs). Four hours after the last injection of CNO, the mice were anesthetized, blood and the liver were collected and then the animals perfused for brain harvesting. Body weight measurements have been performed before and after the 36hrs period of fasting. Another set of Pomc-ires-cre (hM3DGq or mCherry) and WT animals were fasted (36hrs), treated with CNO (5X) and subjected to GTT. DREADD–induced activation of POMCARC neurons has been confirmed by the increased cFos/mCherry expression after CNO treatment only in Pomc-ires-cre animals expressing hM3DGq. We observed that the specific activation of POMCARC neurons did not change the fasting-induced activation of HPA axis. Surprisingly, we observed reduced body weight loss and higher plasma glucose in Pomc-ires-cre animals expressing the hM3DGq and treated with CNO. The GTT showed an impaired glucose tolerance after activation of POMCARC neurons. The increased fasting glucose plasma levels was associated with increased G6pc (Glucose-6-phosphatase) mRNA expression but with no effect on other hepatic gluconeogenic genes. The present study reveals that POMCARC neurons are not involved in the increased HPA axis activity in prolonged fasting conditions. Considering the classical anorexigenic/thermogenic and the glucose-lowering action of POMCARC neurons, the present data reveal an unpredicted reduced body weight loss and impaired glucose tolerance induced by activation of these neurons during fasting. These data reinforce the notion that POMCARC neurons are heterogeneous and might be playing dual effects on energy homeostasis. Of note, because part of ARC neurons shares a common progenitor, some of the functions ascribed to POMC neurons could be mediated by non-POMC neurons expressing the Cre transgene.


2018 ◽  
Vol 10 (02) ◽  
pp. 164-175 ◽  
Author(s):  
A. Bansal ◽  
C. Li ◽  
F. Xin ◽  
A. Duemler ◽  
W. Li ◽  
...  

AbstractExposure to the endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with health abnormalities that persist in subsequent generations. However, transgenerational effects of BPA on metabolic health are not widely studied. In a maternal C57BL/6J mice (F0) exposure model using BPA doses that are relevant to human exposure levels (10 μg/kg/day, LowerB; 10 mg/kg/day, UpperB), we showed male- and dose-specific effects on pancreatic islets of the first (F1) and second generation (F2) offspring relative to controls (7% corn oil diet; control). In this study, we determined the transgenerational effects (F3) of BPA on metabolic health and pancreatic islets in our model. Adult F3 LowerB and UpperB male offspring had increased body weight relative to Controls, however glucose tolerance was similar in the three groups. F3 LowerB, but not UpperB, males had reduced β-cell mass and smaller islets which was associated with increased glucose-stimulated insulin secretion. Similar to F1 and F2 BPA male offspring, staining for markers of T-cells and macrophages (CD3 and F4/80) was increased in pancreas of F3 LowerB and UpperB male offspring, which was associated with changes in cytokine levels. In contrast to F3 BPA males, LowerB and UpperB female offspring had comparable body weight, glucose tolerance and insulin secretion as Controls. Thus, maternal BPA exposure resulted in fewer metabolic defects in F3 than F1 and F2 offspring, and these were sex- and dose-specific.


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