Serum Metabolic Hormones Research Articles

Intermittent energy restriction inhibits tumor growth and enhances paclitaxel response in a transgenic mouse model of endometrial cancer

ObjectiveOverweight/obesity is the strongest risk factor for endometrial cancer (EC), and weight management can reduce that risk and improve survival. We aimed to establish the differential benefits of intermittent energy restriction (IER) and low-fat diet (LFD), alone and in combination with paclitaxel, to reverse the procancer effects of high-fat diet (HFD)-induced obesity in a mouse model of EC. MethodsLkb1fl/flp53fl/fl mice were fed HFD or LFD to generate obese and lean phenotypes, respectively. Obese mice were maintained on a HFD or switched to a LFD (HFD-LFD) or IER (HFD-IER). Ten weeks after induction of endometrial cancer, mice in each group received paclitaxel or placebo for 4 weeks. Body and tumor weights; tumoral transcriptomic, metabolomic and oxylipin profiles; and serum metabolic hormones and chemocytokines were assessed. ResultsHFD-IER and HFD-LFD, relative to HFD, reduced body weight; reversed obesity-induced alterations in serum insulin, leptin and inflammatory factors; and decreased tumor incidence and mass, often to levels emulating those associated with continuous LFD. Concurrent paclitaxel, versus placebo, enhanced tumor suppression in each group, with greatest benefit in HFD-IER. The diets produced distinct tumoral gene expression and metabolic profiles, with HFD-IER associated with a more favorable (antitumor) metabolic and inflammatory environment. ConclusionIn Lkb1fl/flp53fl/fl mice, IER is generally more effective than LFD in promoting weight loss, inhibiting obesity-related endometrial tumor growth (particularly in combination with paclitaxel), and reversing detrimental obesity-related metabolic effects. These findings lay the foundation for further investigations of IER as an EC prevention and treatment strategies in overweight/obesity women.

Effect of a Low-Carbohydrate Diet With or Without Exercise on Anxiety and Eating Behavior and Associated Changes in Cardiometabolic Health in Overweight Young Women.

BackgroundThe effectiveness of low-carbohydrate diets (LCDs) on weight loss and exercise for improving cardiometabolic fitness have been well documented in the literature, but the effects of LCDs and whether adding exercise to a LCD regime could additionally benefit mental health (e. g., by lowering the level of anxiety) and associated changes in eating behavior are less clear in overweight and obese populations. Therefore, this study aimed to investigate the effects of a 4-week LCD with or without exercise on anxiety and eating behavior, and to explore the associations between changes in the psychological state and physiological parameters (i.e., body composition, aerobic fitness, blood pressure, lipid profile, and metabolic hormones).MethodsSeventy-four overweight Chinese women [age: 20.8 ± 3.0 years, body mass index (BMI): 25.3 ± 3.3 kg·m−2] completed the 4-week randomized controlled trial, which included a LCD group (i.e., ~50 g daily carbohydrate intake) with exercise training 5 days/week (LC-EXE, n = 26), a LCD group without exercise training (LC-CON, n = 25) and a control group that did not modify their habitual diets and physical activity (CON, n = 23). Levels of anxiety, eating behavior scores and physiological parameters (i.e., body weight, V̇O2peak, blood pressure, fasting glucose, blood lipids, and serum metabolic hormones including insulin, C-peptide, leptin, and ghrelin) were measured before and after the intervention.ResultsThere were significant reductions in anxiety levels in the LC-EXE compared with the LC-CON group, while no statistical changes were found in eating behaviors in any conditions after the 4-week intervention. Significant reduction in weight (~3.0 kg or 4%, p < 0.01) and decreases in insulin (~30% p < 0.01), C-peptide (~20% p < 0.01), and leptin (~40%, p < 0.01) were found in both LC-CON and LC-EXE groups, but adding exercise to a LCD regime generated no additional effects. There were significant improvements in V̇O2peak (~15% p < 0.01) and anxiety (~25% p < 0.01) in the LC-EXE compared with the LC-CON group, while no statistical differences were found between CON and LC-CON treatments. Further analysis revealed a negative association (r = −0.32, p < 0.01) between changes in levels of anxiety and changes in V̇O2peak in all participates, no other correlations were found between changes in psychological and physiological parameters.ConclusionAlthough the combination of a LCD and exercise may not induce additional reductions in body weight in overweight young females, exercise could be a useful add-on treatment along with a LCD to improve cardiometabolic health and lower anxiety levels.

Relationship among serum metabolic hormones with pregnancy rates to fixed-time artificial insemination in Bos indicus beef females

Two experiments compared body parameters and serum concentrations of GH, IGF-I, and leptin in Bos indicus females based on their pregnancy status to fixed-time artificial insemination (FTAI). In Exp. 1, 226 nulliparous heifers were assigned to a puberty induction protocol (d -35 to d -23), followed by an estrus synchronization and FTAI protocol (d -11 to 0). Heifers received a controlled internal progesterone releasing insert (CIDR) previously used three times on d -35, followed by 0.6 mg of estradiol cypionate and CIDR removal on d -23. Heifers received 2 mg of estradiol benzoate and a CIDR previously used twice on d -11, 12.5 mg of dinoprost tromethamine in addition to CIDR removal, 0.6 mg of estradiol cypionate and a 200 IU of eCG on d -2, followed by FTAI on d 0. Heifer BW and BCS were recorded on d -35, -11, and 30, whereas blood samples were collected on d -35, -23, -11, 0, and 30. In Exp. 2, 821 multiparous lactating Nelore beef cows were assigned to the estrus synchronization and FTAI protocol described in Exp. 1, but received 300 IU of eCG on d -2. Cow BW and BCS were recorded on d -11 and 30, and blood samples were collected on d -11, 0, and 30. In both experiments, pregnancy status was verified via transrectal ultrasonography on d 30. In Exp. 1, heifers that became pregnant had greater (P = 0.03) IGF-I concentrations on d 0 and less (P = 0.05) IGF-I concentrations on d 30 compared to heifers that did not become pregnant (pregnancy status × day; P < 0.01). No differences in BW, BCS, GH and leptin were detected (P ≥ 0.23) according to heifer pregnancy status. In Exp. 2, cows that became pregnant had less (P = 0.03) leptin concentrations on d -11, and less (P = 0.01) IGF-I concentrations on d 30 compared to cows that did not become pregnant (pregnancy status × day; P ≤ 0.05). No differences in BW, BCS, and GH were detected (P ≥ 0.15) according to cow pregnancy status. In summary, serum leptin at the beginning of estrus synchronization was negatively associated with pregnancy rates to FTAI in multiparous cows. A negative relationship was also observed between serum IGF-I during early gestation with pregnancy rates to FTAI across parities. These results provide novel insights on the relationships among metabolic hormones with reproductive performance of B. indicus females.

Mulberry Leaf Flavonoids Improve Milk Production, Antioxidant, and Metabolic Status of Water Buffaloes.

This study was aimed to evaluate the effect of mulberry leaf flavonoids (MLF) on oxidative stress, metabolic hormones, and milk production in Murrah buffaloes. Forty multiparous Murrah buffaloes (4 ± 1 lactations) with similar body weight (average 600 ± 50 Kg) and stage of lactation (90 ± 20 d) were randomly selected for this trial. Four treatment groups (10 buffaloes per group) with different doses of MLF included; control (0 g/d), MLF15 (15 g/d), MLF30 (30 g/d), and MLF45 (45 g/d). Buffaloes were fed with total mix ration consisting of grass (Pennisetum purpureum schum), brewery's grain and concentrate mixture for 5 weeks. Meteorological data including ambient temperature and relative humidity were recorded using the online dust monitoring system to calculate temperature-humidity index (THI). After 1 week of the adaptation, milk yield was recorded daily while physiological parameters (respiratory rate, rectal, and body surface temperature), and milk composition were measured weekly. At the end of the trial, blood samples were collected to analyze serum metabolic hormones including estradiol (E2), growth hormone (GH), prolactin (PRL), Tri-iodothyronine (T3), and Thyroxine (T4). Moreover, serum heat shock proteins (HSP), antioxidants enzymes including malondialdehyde (MDA), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and blood biochemical indices were also analyzed. Results revealed a decrease (P = 0.012) in serum MDA level while increasing (P < 0.01) the HSP and serum GHS-Px contents in supplemented buffaloes. Treatment showed a linear and quadratic decrease (p = 0.001) in the serum T-AOC while reducing CAT contents linearly (p = 0.012) as compared to the control. However, no effect of treatment on serum SOD content was observed. Treatment resulted a linear increase (p = 0.001) in serum GH and PRL hormones while increasing serum E2 levels linearly (P < 0.001) and quadratically (P = 0.025). Treatment increased (p = 0.038) the daily milk yield as compared to the control. However, increase (P < 0.05) in serum T3 and T4 contents, fat corrected milk (4%) and milk protein (%) was observed only in MLF45. Moreover, we observed no change in serum biochemical indices except insulin which linearly increased (p = 0.002) in MLF45. Our findings indicated that MLF at 45 g per day is an appropriate level to enhance milk performance and alleviate heat stress in buffaloes.

Dynamics of breast tumor incidence, tumor volume and serum metabolic hormones in calorie restricted rats

ABSTRACT Reports of the effects of calorie restriction on tumors after the tumor has developed are uncommon and limited to a few tumor types. We investigated the effects of calorie restriction on tumor growth in breast cancer after tumor growth had progressed. We used the N-nitroso-N-methylurea (NMU) induced breast cancer model in rats. In addition to a healthy control group (C), rats with 10 − 12 mm tumors were divided into three groups: cancer control group (CC), alternate day feeding group (ADF) and calorie restriction group (CR-50%). At the end of the experimental period the volume of tumors was decreased in the CR-50% group compared to the CC group. Serum adiponectin concentrations for the C and ADF groups were higher than for the CC group. All tumors of the CR-50% group were benign. The highest incidence of malignant and invasive tumors occurred in the CC group. A 50% calorie restriction appears to be an effective dietary intervention for advanced tumors.

Daily consumption of monoglucosyl-rutin prevents high-fat diet-induced obesity by suppressing gastric inhibitory polypeptide secretion in mice

Background: Alpha monoglucosyl-rutin (4G-α-D-glucopyranosyl rutin, αMR) has been shown to stimulate antioxidant defenses and anti-glycation. We evaluated the effects of αMR on body weight gain in mice.Methods: Male C57BL/6J mice were divided into four groups: Control low-fat diet, low-fat diet + 0.5% αMR, high-fat diet, and high-fat diet + 0.5% αMR. Blood chemistry, hepatic lipids, and serum metabolic hormones and cytokines were evaluated after 4 and 13 weeks.Results: After 6 weeks, the high-fat diet group gained more weight than the low-fat diet group. Supplementing the high-fat diet with αMR suppressed weight gain by week 13. Visceral fat weight was higher in the high-fat diet group on weeks 4 and 13, while αMR supplementation inhibited increase on week 13 but not on week 4. Serum levels of gastric inhibitory polypeptide were higher in the high-fat-diet group than in the low-fat-diet group. αMR supplementation inhibited this elevation and regulated levels of serum leptin and hepatic triglycerides.Conclusion: For the first time, we demonstrated how daily consumption of αMR inhibits diet-induced visceral fat accumulation by regulating the secretion of gastric inhibitory polypeptide, which thereby prevents excess weight gain. Therefore, αMR may be a promising potential functional food.Keywords: Anti-obesity; gastric inhibitory polypeptide; mouse; alpha monoglucosyl-rutin; quercetin

Energy Balance Modulation Impacts Epigenetic Reprogramming, ERα and ERβ Expression, and Mammary Tumor Development in MMTV-neu Transgenic Mice.

The association between obesity and breast cancer risk and prognosis is well established in estrogen receptor (ER)-positive disease but less clear in HER2-positive disease. Here, we report preclinical evidence suggesting weight maintenance through calorie restriction (CR) may limit risk of HER2-positive breast cancer. In female MMTV-HER2/neu transgenic mice, we found that ERα and ERβ expression, mammary tumorigenesis, and survival are energy balance dependent in association with epigenetic reprogramming. Mice were randomized to receive a CR, overweight-inducing, or diet-induced obesity regimen (n = 27/group). Subsets of mice (n = 4/group/time point) were euthanized after 1, 3, and 5 months to characterize diet-dependent metabolic, transcriptional, and epigenetic perturbations. Remaining mice were followed up to 22 months. Relative to the overweight and diet-induced obesity regimens, CR decreased body weight, adiposity, and serum metabolic hormones as expected and also elicited an increase in mammary ERα and ERβ expression. Increased DNA methylation accompanied this pattern, particularly at CpG dinucleotides located within binding or flanking regions for the transcriptional regulator CCCTC-binding factor of ESR1 and ESR2, consistent with sustained transcriptional activation of ERα and ERβ. Mammary expression of the DNA methylation enzyme DNMT1 was stable in CR mice but increased over time in overweight and diet-induced obesity mice, suggesting CR obviates epigenetic alterations concurrent with chronic excess energy intake. In the survival study, CR elicited a significant suppression in spontaneous mammary tumorigenesis. Overall, our findings suggest a mechanistic rationale to prevent or reverse excess body weight as a strategy to reduce HER2-positive breast cancer risk. Cancer Res; 77(9); 2500-11. ©2017 AACR.

A case report of recovery of menstrual function following a nutritional intervention in two exercising women with amenorrhea of varying duration

Increasing caloric intake is a promising treatment for exercise-associated amenorrhea, but strategies have not been fully explored. The purpose of this case report was to compare and contrast the responses of two exercising women with amenorrhea of varying duration to an intervention of increased energy intake. Two exercising women with amenorrhea of short (3 months) and long (11 months) duration were chosen to demonstrate the impact of increased caloric intake on recovery of menstrual function and bone health. Repeated measures of dietary intake, eating behavior, body weight, body composition, bone mineral density, resting energy expenditure, exercise volume, serum metabolic hormones and markers of bone turnover, and daily urinary metabolites were obtained. Participant 1 was 19 years old and had a body mass index (BMI) of 20.4 kg/m2 at baseline. She increased caloric intake by 276 kcal/day (1,155 kJ/day, 13%), on average, during the intervention, and her body mass increased by 4.2 kg (8%). Participant 2 was 24 years old and had a BMI of 19.7 kg/m2. She increased caloric intake by 1,881 kcal/day (7,870 kJ/day, 27%) and increased body mass by 2.8 kg (5%). Resting energy expenditure, triiodothyronine, and leptin increased; whereas, ghrelin decreased in both women. Resumption of menses occurred 23 and 74 days into the intervention for the women with short-term and long-term amenorrhea, respectively. The onset of ovulation and regular cycles corresponded with changes in body weight. Recovery of menses coincided closely with increases in caloric intake, weight gain, and improvements in the metabolic environment; however, the nature of restoration of menstrual function differed between the women with short-term versus long-term amenorrhea.

Circulating Metabolic Hormones During the Peripubertal Period and Their Association with Testicular Development in Bulls

The objective of the present study was to characterize changes in serum metabolic hormones concentrations from 20 weeks before to 20 weeks post-puberty in bulls and to investigate the associations of metabolic hormones concentrations with testicular development. Leptin concentrations increased from 16 weeks before puberty to 8 weeks post-puberty and insulin concentrations increased from puberty to 8 weeks post-puberty. Growth hormone concentrations decreased after 4 weeks post-puberty, whereas IGF-I concentrations increased from 8 weeks before puberty to 8 weeks post-puberty. During this period, testicular growth was accelerated and testosterone secretion increased substantially, without any significant changes in gonadotropin secretion. Monthly circulating concentrations of leptin, IGF-I and insulin accounted for 63% of the variation in scrotal circumference and 59% of the variation in paired testes volume. In conclusion, the secretion of metabolic hormones was not associated with changes in gonadotropins concentrations. Furthermore, the associations of leptin, IGF-I and insulin concentrations with testes size indicated that these hormones might be involved in a gonadotropin-independent mechanism regulating the testicular development in peripubertal bulls.

Effect of improved nutrition during calfhood on serum metabolic hormones, gonadotropins, and testosterone concentrations, and on testicular development in bulls

The objective of the present study was to evaluate the effects of improved nutrition during calfhood on serum metabolic hormones, gonadotropins and testosterone concentrations, and on sexual development in bulls. Bulls received high ( n = 17) or control nutrition ( n = 16) diets from 10 to 30 week of age and the same control nutrition diet from 31 to 74 week of age. Improved nutrition during calfhood resulted in a more sustained period of elevated LH secretion (pulse frequency and total secretion in 10 h) during the early gonadotropin rise. GnRH-stimulated LH secretion was not affected by diet, indicating that pituitary responsiveness was not altered; therefore, improved nutrition had direct effects on GnRH secretion by the hypothalamus. Insulin and insulin-like growth factor-I (IGF-I) concentrations were greater during calfhood in bulls receiving high nutrition, indicating that these metabolic hormones might be involved in regulating GnRH and LH secretion. Improved nutrition also resulted in increased testosterone secretion that was associated with greater circulating IGF-I concentrations, suggesting a role for this metabolic hormone in regulating Leydig cell number and function. Furthermore, improved nutrition during calfhood resulted in greater testicular weight and sperm production in mature bulls, indicating that increased LH secretion during calfhood, and increased IGF-I and testosterone concentrations during calfhood and peripubertal period were associated with greater testicular cell proliferation and enhanced function.

Effect of nutrition during calfhood and peripubertal period on serum metabolic hormones, gonadotropins and testosterone concentrations, and on sexual development in bulls

The objective of the present study was to characterize the effects of nutrition on circulating concentrations of metabolic hormones, gonadotropins, and testosterone during sexual development in bulls. Nutrition regulated the hypothalamus–pituitary–testes axis through effects on the GnRH pulse generator in the hypothalamus and through direct effects on the testes. Pituitary function (gonadotropin secretion after GnRH challenge) was not affected by nutrition. However, nutrition affected LH pulse frequency and basal LH concentration during the early gonadotropin rise (10–26 weeks of age). There were close temporal associations between changes in insulin-like growth factor-I (IGF-I) concentrations and changes in LH pulse frequency, suggesting a role for IGF-I in regulating the early gonadotropin rise in bulls. The peripubertal increase in testosterone concentration was delayed in bulls with lesser serum IGF-I concentrations (low nutrition), suggesting a role for IGF-I in regulating Leydig cell function. Serum IGF-I concentrations accounted for 72 and 67% of the variation in scrotal circumference and paired-testes volume, respectively (at any given age), indicating that IGF-I may regulate testicular growth. Bulls with a more sustained elevated LH pulse frequency during the early gonadotropin rise (high nutrition) had greater testicular mass at 70 weeks of age relative to the control group (medium nutrition), despite no differences in metabolic hormone concentrations after 26 weeks of age. Therefore, gonadotropin-independent mechanism regulating testicular growth might be dependent on previous gonadotropin milieu.

Endocrine responses and body composition changes during feed restriction and realimentation in young bulls2

Changes in serum metabolic hormones, carcass composition, and body weight gains were examined in 21 Angus bulls (9 mo old) subjected to feed restriction and realimentation. They were allotted to three feeding regimens: 1) control (CON); 2) restricted (REST); and 3) realimented (REAL). The CON group was fed 3.2% of their body weight; the REST group was fed 1.5%. The REAL group was fed the restricted diet (1.5% BW) for 84 d then fed the control diet (3.2% BW) until slaughter. The CON and REAL groups were slaughtered at approximately 400 kg and the REST group at 346 kg. For the experiment, average daily gains (kg/d) were different (P < .05) (CON = 1.60; REAL = 1.35; REST = .64). Bulls were bled every 20 min for 6 h on d 14, 70, 98, and 127 of the experiment. Overall carcass characteristics (yield grade, muscle area, marbling) and chemical analysis of 9-10-11 rib sections indicated changes in quantity and percentages of protein and fat commensurate with the dietary intake treatments. The REST group had the least lean and fat (P < .05); the REAL group had less fat than (P < .05) but the same amount of lean (P > .05) as the CON group. Serum GH was higher in the REST than in the CON group (P < .05). In the REAL group, serum GH values rose to a level similar to that of the REST group; realimentation lowered serum GH (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of graded levels of bentonite on serum clinical profiles, metabolic hormones, and serum swainsonine concentrations in lambs fed locoweed (Oxytropis sericea)1

To determine which clay minerals have the potential to bind swainsonine, an in vitro screening procedure was conducted. Twenty compounds were screened in one replicated in vitro trial. A commercially available bentonite bound approximately 10% swainsonine and was chosen for use in a subsequent lamb feeding trial. Twenty fine-wool lambs (30.5 +/- .7 kg) were assigned to one of five treatments (four lambs/treatment). Treatments included 1) positive control, 100% sorghum sudangrass hay, 2) 85% sorghum sudangrass:15% locoweed (Oxytropis sericea, 430 ppm [DM basis] of swainsonine) +0 g of bentonite, 3) Treatment 2 + 14 g of bentonite, 4) Treatment 2 + 28 g of bentonite, and 5) Treatment 2 + 42 g of bentonite. Lambs were fed the experimental diets for 35 d and were then fed the positive control diet for an additional 21 d. Lambs were weighted and blood was collected via jugular venipuncture weekly from d 0 through 56. On d 35, additional blood samples were collected 1, 2, 4, and 8 h after feeding. Weekly blood samples were analyzed for serum clinical chemistry profiles, and additional blood samples collected on d 35 were analyzed for serum metabolic hormones and serum swainsonine concentrations. Within 1 wk, serum alkaline phosphatase and glutamic oxaloacetic transaminase activities increased markedly (P < .05) in lambs fed locoweed. Serum insulin, growth hormone, and prolactin concentrations were not affected by feeding locoweed, but serum triiodothyronine and thyroxine concentrations were decreased by approximately 50% (P < .05) in lambs fed locoweed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of lasalocid and monensin plus tylosin on serum metabolic hormones and clinical chemistry profiles of beef steers fed a 90% concentrate diet.

Fourteen crossbred beef steers (average initial BW 313 +/- 13.1 kg) fed a 90% concentrate diet (as-fed basis) were used to evaluate effects of ionophores on serum metabolic hormones and clinical chemistry profiles. Treatments were no ionophore (C; four steers), lasalocid (L; 33 mg/kg of diet; five steers), and monensin (33 mg/kg of diet) plus tylosin (11 mg/kg of diet; MT; five steers). All steers were adapted to the 90% concentrate diet, after which treatments were applied and blood was sampled via jugular catheters on d 7, 35, 63, 91, and 119 of the trial at 0, 1, 2, 3, 4, 6, 8, and 10 h after feeding. Averaged over sampling days, serum glucose concentrations did not differ (P > .10) among treatments at any sampling time (treatment x sampling time, P < .05). Average across sampling days and times, serum growth hormone, insulin, cholesterol, and triglyceride concentrations did not differ (P > .10) among treatments. No major effects of ionophores were noted for serum enzymes or protein fractions. Averaged over sampling times within day (treatment x day interaction, P < .10), both L and MT increased (P < .05) serum Ca and Na concentrations on d 91 and 119 compared with C. Serum inorganic P was increased (P < .10) for L vs MT and for ionophore treatments compared with C (P < .10) on several occasions (treatment x day x sampling time interaction, P < .05). Results suggest that ionophores do not cause dramatic changes in serum metabolic hormones or clinical chemistry profiles; however, monensin and lasalocid altered serum minerals in beef steers fed a high-concentrate diet.