Body Weight Cycle Research Articles

Impact of home-based aerobic training combined with food orientation on food consumption, daily physical activity and cardiorespiratory fitness among breast cancer survivors: six-month clinical trial.

Anticancer treatment gives rise to adverse effects such as increased pain and changes to body weight and menstrual cycles, with negative effects on activities of daily living. To analyze the effect of food orientation combined with supervised (face-to-face, FF) versus home-based (HB) aerobic training on lifestyle (food consumption and daily physical activity (PA) levels), body composition, metabolic profile and cardiorespiratory fitness, among breast cancer survivors. Clinical trial study (six months) conducted at a public university in Presidente Prudente, Brazil. Twenty-three female breast cancer survivors (40-75 years old) were allocated to aerobic training groups, either FF or HB. Both groups were trained and received food orientation. They were evaluated through a dietary record, ergometric treadmill test and blood test and the Baecke questionnaire. After six months, both groups had reduced their lipid levels, total energy consumption and polyunsaturated fat intake, and had increased their PA levels and treadmill test durations. However, only the HB showed reduced carbohydrate percentage and increased folic acid; and only the FF showed reduced lipid, saturated fat and sodium levels, along with increased carbohydrate and protein levels. No differences in body composition or metabolic profile were found. These results demonstrated the feasibility of HB aerobic training. In isolation, HB showed greater regulation of carbohydrate percentage and increased folic acid levels. Moreover, these breast cancer survivors presented improvements in food consumption, PA levels and cardiorespiratory fitness, while also maintaining their body composition and metabolic profile after the intervention, independent of the group.

Neuroendocrine Basis for Disrupted Ovarian Cyclicity in Females During Chronic Undernutrition: A Mouse Model

Chronic undernutrition is a type of metabolic stress that impairs reproduction across species and, in women, is implicated in the development of functional hypothalamic amenorrhea. Although the tight coupling of energy balance to reproductive capacity is recognized in principle, the neuroendocrine loci and molecular mechanisms that mediate ovarian cycle dysfunction during undernutrition remain poorly understood. Ovarian cyclicity is dependent on a population of kisspeptin (Kiss1) neurons in arcuate nucleus (ARCKiss1) for luteinizing hormone (LH) pulses and in the anteroventral periventricular nucleus (AVPVKiss1) for LH surge secretion. Here, we present a series of studies in which we tested the hypothesis that inhibition of both Kiss1 cell populations underlies the impairment of the cycle by undernutrition. During a baseline period, body weight, feed intake, and ovarian cycle stage (via vaginal cytology) were evaluated in female c57bl6 mice. Then, animals were randomly assigned into one of two groups (n=6-8/grp): 1) ad libitum fed controls or 2) feed restricted (70% of feed consumed during the baseline period). Control animals displayed clear and regular cycles throughout the 4-week treatment period. In contrast, feed restriction caused a significant and rapid cessation of ovarian cyclicity (4.8±0.3 vs. 1.5±0.5 estrus cycles/4 weeks; control vs. restricted, p<0.05), causing all females to enter and remain mostly in diestrus. Based on these results, we conducted two experiments to directly test the hypothesis that undernutrition inhibits both modes of LH secretion (and both Kiss1 cell populations) using two well-defined estradiol (E) replacement paradigms. We first evaluated LH pulses in mice that were ovariectomized and implanted subcutaneously with a pellet containing a diestrus level of E (100 ng, OVX+LowE). Following 3 days of feed restriction or control diet (n=3/grp), serial blood samples were collected every 8 min for 88 min. Undernutrition prevented LH pulses and significantly reduced mean LH (5.2±0.6 vs. 0.6±0.2 ng/mL; control vs. restricted, p<0.05). Fixed neural tissue was evaluated by immunohistochemistry to determine whether undernutrition impairs ARCKiss1 neuronal activation, using c-Fos as a marker. The percent of ARCKiss1 neurons expressing cFos was reduced by 90% (p<0.05). We next evaluated the LH surge. After 3 days, control or feed restricted mice were OVX and implanted subcutaneously with a surge-inducing estradiol implant (OVX+HighE, 1 µg, n=3-4/grp). Undernutrition completely blocked the E-induced LH surge (1.9±0.3 vs. 0.2±0.02 ng/mL; control vs. restricted, p<0.05) and diminished Kiss1 mRNA abundance in micropunches of the AVPV (42%, p<0.05). Collectively, these studies clearly show that undernutrition impairs both ARCKiss1 control of LH pulses and AVPVKiss1 induction of the LH surge, via mechanisms that remain to be identified.

Arginase-1 deficiency in neural cells does not contribute to neurodevelopment or functional outcomes after sciatic nerve injury

Arginase-1 (Arg1) is an enzyme controlling the final step of the urea cycle, with highest expression in the liver and lower expression in the lungs, pancreas, kidney, and some blood cells. Arg1 deficiency is an inherited urea cycle disorder presenting with neurological dysfunction including spastic diplegia, intellectual and growth retardation, and encephalopathy. The contribution of Arg1 expression in the central and peripheral nervous system to the development of neurological phenotypes remains largely unknown. Previous studies have shown prominent arginase-1 expression in the nervous system and post-peripheral nerve injury in mice, but very low levels in the naïve state. To investigate neurobiological roles of Arg1, we created a conditional neural (n)Arg1 knockout (KO) mouse strain, with expression eliminated in neuronal and glial precursors, and compared them to littermate controls. Long-term analysis did not reveal any major differences in blood amino acid levels, body weight, or stride gait cycle from 8 to 26-weeks of age. Brain structure measured by magnetic resonance imaging at 16-weeks of age observed only a significant decrease in the volume of the mammillary bodies. We also assessed whether nArg1, which is expressed by sensory neurons after injury, may play a role in regeneration following sciatic nerve crush. Only subtle differences were observed in locomotor and sensory recovery between nArg1 KO and control mice. These results suggest that arginase-1 expression in central and peripheral neural cells does not contribute substantially to the phenotypes of this urea cycle disorder, nor is it likely crucial for post-injury regeneration in this mouse model.

Effect of urolithins A and B on ectopic endometrial growth in a murine model of endometriosis.

Endometriosis is an often painful disease in reproductive-aged women, in which endometrial-like tissue grows outside the uterine cavity. Since the limited current therapeutic alternatives fail in alleviating the symptoms and based on our previous research in in vitro models using the same compounds as the ones used in the present study, we aimed to evaluate the effects of urolithins A (UA) and B (UB) on the growth and survival of endometriotic-like lesions in a murine model of endometriosis. Female BALB/C mice were surgically induced with endometriosis and treated with 2.5 mg kg-1 day-1 intraperitoneal UA or UB. The mice were monitored daily and weighed and the estrous stage was determined. After 28 days of treatment, lesions were counted, measured, excised, and fixed. Both urolithins proved not to affect the estrous cycle or body weight of the mice. UA completely prevented endometriotic-like lesions, while UB diminished the implant volume (p < 0.05). Treatment also reduced epithelial and stromal cell proliferation within the implants (p < 0.001 and p < 0.01, respectively) and apoptosis was enhanced (p < 0.05 and p < 0.01, respectively). These results are promising and reveal that urolithins A and B, separately, have a beneficial effect on the overall endometriotic growth without affecting the body weight or estrous cycle.

Hyperandrogenemia alters mitochondrial structure and function in the oocytes of obese mouse with polycystic ovary syndrome

Hyperandrogenemia in an obese PCOS mouse model results in altered glucose/insulin metabolism and mitochondrial structure and function in the oocytes, in part explaining adverse outcomes and inheritance patterns seen in PCOS. To study the oocyte quality by means of mitochondrial structure and function in a well-established classic PCOS mouse model. Animal study using an obese PCOS mouse model compared with control. Animal research facility in a tertiary care university hospital setting. C57/B6J mice. Three week old mice had subdermal implants of DHT controlled release pellet or placebo for 90 days. The mouse model was validated by performing glucose tolerance test, HbA1c levels, body weight and estrous cycle analyses. Oocytes were subsequently isolated and were used to investigate mitochondrial membrane potential, oxidative stress, lipid peroxidation, ATP production, mtDNA copy number, transcript abundance, histology and electron microscopy. Results showed glucose intolerance and hyperinsulinemia along with dysregulated estrus cycle. Analysis of the oocytes demonstrated impaired inner mitochondrial membrane function, increased ATP production and mtDNA copy number, altered RNA transcript abundance and aberrant ovarian histology. Electron microscopy of the oocytes showed severely impaired mitochondrial ultrastructure. The obese PCOS mouse model shows a decreased oocyte quality related to impaired mitochondrial function.

Association between weight cycling and risk of developing diabetes in adults: A systematic review and meta-analysis.

Aims/IntroductionIn this meta‐analysis, we aimed to explore the association between bodyweight cycling (weight fluctuation) and the risk of developing diabetes.Materials and MethodsWe analyzed data from eligible cohort studies that assessed the association between weight cycling in adults and the risk of developing diabetes from online databases PubMed, Cochrane Library and EMBASE databases (1966 to April 2020). We pooled data using relative risks (RRs) with a random effects model.ResultsA total of 14 studies involving 253,766 participants, including 8,904 diabetes events, were included. One study included eight independent reports, resulting in 21 reports in 14 studies. Summary analysis showed that individuals who suffered weight cycling had a higher risk of diabetes (RR 1.23. 95% confidence interval 1.07–1.41; P = 0.003). However, the association between weight cycling and the risk of developing diabetes was not observed in obese participants (body mass index ≥30 kg/m2; P = 0.08).ConclusionsThe present meta‐analysis showed that weight cycling was a strong independent predictor of new‐onset diabetes. Future studies are required to detect the causal links between weight cycling and the risk of developing diabetes.

Short-Term Sprint Interval Training Increases Maximal Oxygen Uptake Without Changing Maximal Cardiac Output

Traditional moderate intensity continuous training increases maximal oxygen uptake (VO2max). This effect is primarily attributed to an increased maximal cardiac output (Qmax), as predicted by the Fick principle. Sprint interval training (SIT) increases VO2max similar to MICT, often despite a lower training volume, but the effect on Qmax is unclear. PURPOSE: To determine the effect of 6 sessions of SIT over 2 wk on VO2max, Qmax and exercise performance in healthy, untrained adults [n=12 (9 females); 21±2 y; mean±SD]. METHODS: Training was performed on a cycle ergometer and involved a 2-min warm-up (50 W), 3 x 20-s ‘all-out’ bouts interspersed with 2-min of recovery (50 W), and a 3-min cool-down (50 W). VO2max was determined using a ramp test to exhaustion. Qmax was subsequently determined using inert gas rebreathing (Innocor) over a 2-min period of exercise performed at 90% of the peak work rate attained during the VO2max test. Pilot testing confirmed this protocol elicited VO2max over the 2-min period of Qmax measurement. The performance test was a 2 kJ/kg body weight cycling time trial. All measurements were performed twice at baseline, and reproducibility determined as a coefficient of variation (CV). The CV for VO2max, Qmax and time trial performance was 5.8, 4.7 and 4.2%, respectively. Pre- and post-training measurements were compared using a paired t-test. RESULTS: VO2max increased after SIT from 37.0±7.3 to 40.7±8.3 ml/kg/min (p<0.001), but Qmax was unchanged (17.2±3.8 vs 17.7±4.6 L/min; p>0.05). Exercise performance improved after SIT from 1040±247 to 938±238 s (p<0.001). Absolute VO2max was positively correlated with Qmax (r2 = 0.86, p < 0.001). CONCLUSION: Six sessions of SIT increased VO2max without changing Qmax in previously untrained individuals. These data support previous suggestions that the early increase in VO2max after SIT may be due mainly to peripheral responses (i.e., enhanced oxygen extraction by skeletal muscle), rather than a central change in blood oxygen delivery. Supported by NSERC

Prenatal androgen induced lean PCOS impairs mitochondria and mRNA profiles in oocytes.

Polycystic ovary syndrome (PCOS) is the most common ovulatory defect in women. Although most PCOS patients are obese, a subset of PCOS women are lean but show similar risks for adverse fertility outcomes. A lean PCOS mouse model was created using prenatal androgen administration. This developmentally programmed mouse model was used for this study. Our objective was to investigate if mitochondrial structure and functions were compromised in oocytes obtained from lean PCOS mouse. The lean PCOS mouse model was validated by performing glucose tolerance test, HbA1c levels, body weight and estrous cycle analyses. Oocytes were isolated and were used to investigate inner mitochondrial membrane potential, oxidative stress, lipid peroxidation, ATP production, mtDNA copy number, transcript abundance and electron microscopy. Our results demonstrate that lean PCOS mice have similar weight to that of the controls but exhibit glucose intolerance and hyperinsulinemia along with dysregulated estrus cycle. Analysis of their oocytes show impaired inner mitochondrial membrane function, elevated reactive oxygen species (ROS) and increased RNA transcript abundance. Electron microscopy of the oocytes showed impaired mitochondrial ultrastructure. In conclusion, the lean PCOS mouse model shows a decreased oocyte quality related to impaired mitochondrial ultrastructure and function.

The Effect of Estradiol Administration on Muscle Mass Loss and Cachexia Progression in Female Apc Min/+ Mice.

Cancer cachexia is a multifactorial muscle wasting condition characterized by severe body weight and muscle mass loss which is secondary to chronic disease. The mechanistic examination of cachexia has predominately focused on the male phenotype and created significant gaps in understanding cachexia progression in the female. Female hypogonadism can accompany cancer cachexia and is characterized by reduced circulating 17ß-estradiol and uterine atrophy. Estrogen has known functions in skeletal muscle homeostasis involving the regulation of muscle protein turnover, cellular stressors, and oxidative metabolism. However, 17ß-estradiol's ability to regulate cachexia progression in the female is not known. The purpose of this study was to determine the effect of gonadal function and estradiol administration on muscle mass loss and cachexia progression in female ApcMin/+ mice.Methods: Female C57BL/6 (B6; N = 82) and ApcMin/+ (MIN; N = 88) mice were used in two separate experiments. In experiment 1, mice were sacrificed at either 12 (N = 20) or 20 (N = 41) weeks of age. Body weight and estrous cycle presence was determined weekly. In experiment 2, B6 and MIN mice were randomly allocated to: Control (N = 17), received E2 pellet (E2, N = 18), ovariectomy surgery (OVX; N = 19) or ovariectomy surgery with E2 pellet (OVX + E2; N = 21). 17ß-estradiol was administered through an implanted slow-releasing pellet (0.1 mg). In estrogen and ovariectomy experiments, food intake, and functional outcomes were recorded 1 week prior to sacrifice.Results: We report that E2 administration prevented body weight loss, muscle mass loss, cage inactivity, and grip strength loss associated with cachexia. In skeletal muscle, E2 reduced skeletal muscle AMPK phosphorylation, improved mTORC1 signaling, and prevented mitochondrial dysfunction.Conclusion: Our results demonstrate a role for 17ß-estradiol for the prevention of skeletal muscle mass loss in female tumor bearing mice. Furthermore, 17ß-estradiol prevented cachexia's disruption in skeletal muscle signaling involving AMPK and mTORC1, in addition to improving mitochondrial function in female tumor bearing mice.

Anti-androgenic and insulin-sensitizing actions of Nigella sativa oil improve polycystic ovary and associated dyslipidemia and redox disturbances

Aim: Nigella sativa oil has been shown to improve metabolic syndrome-associated dyslipidemia and oxidative stress. Effects of N. sativa oil on letrozole-induced polycystic ovary syndrome (PCOS)-associated hormonal, metabolic, redox, and lipid dysregulation in rats were investigated. Methods: Female Sprague-Dawley rats were randomly assigned into four groups (n=10 per group): control, PCOS, and PCOS treated with N. sativa oil (5 mL/kg/day or 10 mL/kg/day) once daily p.o. starting at day 7 after the commencement of letrozole (1mg/kg) until day 56. Body weight and estrous cycle were recorded starting from days 7 and 28 respectively until day 56. Rats were dissected and serum and ovaries were collected for biochemical and histomorphological assessments. Results: N. sativa oil (10 mL/kg/day) treatment significantly increased: number of rats undergoing regular cycle (80% vs 20%; p< 0.05), average number of regular cycles (5.00±0.59 vs 0.20±0.42; p< 0.05), appearance of corpus luteum; but reduced number of cystic follicles (7.60±1.51 vs 6.10±0.19; p< 0.05) in PCOS rats. Body weight was also reduced by the oil in PCOS rats. However, ovarian weight, granulose and theca cells layers showed no significant change. The oil also restored altered circulating levels of gonadotropins, steroids and reduced fasting blood glucose. The ovarian total cholesterol, triglycerides, low density lipoprotein-cholesterol, malondialdehyde were markedly reduced while insulin sensitivity and ovarian high density lipoprotein-cholesterol, superoxide dismutase and glutathione peroxidase activities were greatly increased. Conclusion: N. sativa oil improved polycystic ovarian-morphology and metabolic disorders via its anti-androgenic and insulin-sensitizing actions to ameliorate PCOS-associated dyslipidemia and redox disturbances.

Effect of Vitex negundo L. seeds in letrozole induced polycystic ovarian syndrome

The clinical management of PCOS is multifaceted but often unsatisfactory. The aim of the current study is to evaluate the effect of Vitex negundo L. in the letrozole-induced polycystic ovarian syndrome. Female Sprague-Dawley rats were divided into six groups, each containing 6 animals. Group I (Control) daily received 1% carboxymethylcellulose (CMC) suspension as a vehicle control. Letrozole (1 mg/kg) was administered per orally (p.o) for a period of 21 days for the induction of PCOS in Group II to VI. PCOS induced animals were treated with aqueous (Group III - 200 mg/kg and IV- 400 mg/kg) and hydroalcoholic extract (Group V- 200 mg/kg and VI- 400 mg/kg) of Vitex negundo up to 66 days using 0.5% w/v CMC as the vehicle. Body weight and estrous cycle phase were measured every day. Blood samples were collected on 0, 21 and 66 days for the measurement of fasting blood glucose, lipid profile, LH, FSH and hormonal level. Oral glucose tolerance test was performed to study insulin resistance effect. Toxicity markers; SGOT, SGPT, and creatinine also measured at the end of the study. The administration of Letrozole led to an abnormality in serum sex steroid profile, lipid profile, glucose and estrous cycle. It was able to successfully exert its protective effect by restoring parameters to the normal level and disappearance of cysts in ovaries. This can be attributed to phyto-components present in the extract. The aqueous and hydro-alcoholic extracts of seeds of Vitex negundo showed significant amelioration of Letrozole induced PCOS.

Melatonin-independent Photoperiodic Entrainment of the Circannual TSH Rhythm in the Pars Tuberalis of the European Hamster.

Adaptation of biological rhythms to a seasonal environment in circannual mammals is achieved via the synchronization of intrinsic circannual rhythms to the external year by photoperiod. In mammals, the photoperiodic information is integrated to seasonal physiology via the pineal hormone melatonin regulation of pars tuberalis (PT) TSHβ expression and its downstream control of hypothalamic dio2 gene expression. In the circannual European hamster, however, photoperiodic entrainment of the circannual clock is possible in pinealectomized animals. The present study explores whether the TSHβ expression in the PT and the downstream hypothalamic pathways are regulated by photoperiod in European hamsters in the absence of melatonin. All animals were kept on an accelerated photoperiodic regime, which compressed the natural year to a 6-month cycle. Sham-operated European hamsters and half of the pinealectomized European hamsters entrained their annual cycle in reproduction, body weight, and activity pattern to this cycle, whereas the other half of the pinealectomized animals followed only each second cycle. In all animals, PT TSHβ and hypothalamic dio2 expressions were higher in hamsters displaying a summer physiological state than in those in winter state. Moreover, in agreement with their seasonal state, reproductive animals (summer state) showed higher expression of rfrp and lower expression of kiss1-genes encoding central regulators of the reproductive axis-than those animals in reproductive quiescence (winter state), indicating the hypothalamic integration of the photoperiodic signal even in pinealectomized animals. The appropriate occurrence of a well-characterized activity pattern indicative of a so-called sensitive phase to short photoperiod suggested that the SCN constructs the melatonin-independent photoperiodic message. This message is sufficient to entrain the circannual rhythm in TSHβ expression in the PT and the downstream hypothalamic neuroendocrine pathway through a yet unknown pathway. These results reinforce the hypothesis that the PT is the site for the integration of circannual and photoperiodic information.

Body Weight Cycling with Identical Diet Composition Does Not Affect Energy Balance and Has No Adverse Effect on Metabolic Health Parameters.

Background: Body weight (BW) cycling, the yo-yo effect, is generally thought to have adverse effects on human metabolic health. However, human and animal experiments are limited in number and do not provide clear answers, partly due to large variations in experimental design, parameters measured, and definitions of BW cycling. Here, we examined the effect of repetitive BW cycling versus single- and non-cycling control groups, without alterations in diet composition, on steady state BW and metabolic parameters. Methods: We induced well-defined BW cycles on a semi-purified high fat diet in C57BL/6J mice, a well-described animal model for diet-induced obesity, and measured energy expenditure and relevant metabolic parameters. Results: Our setup indeed resulted in the intended BW changes and always reached a stage of energy balance. A history of weight cycling did not result in increased BW or fat mass compared with the control group, nor in deteriorated serum concentrations of glucose, adipokines and serum triglyceride and free fatty acid (FFA) concentrations. If anything, BW tended to be reduced, presumably because of a reduced overall energy intake in BW cycling animals. Conclusion: Repeated cycling in BW without changes in diet composition does not lead to impaired metabolic health nor increased BW (gain).

Maternal Overweight Disrupts the Sexual Maturation of the Offspring.

The aims of the present work were to study the effect of maternal overweight and obesity on the ovarian reserve, follicular development, and ovulation of the offspring and to assess whether this maternal condition alters oocyte integrity. To this end, female offspring from rats fed standard (OSD) or cafeteria (OCD) diet were used. Body weight, vaginal opening, and estrous cycle were recorded and ovaries were obtained on the day of the second estrus. In addition, ovarian weight, ovulation rate (measured by the number of oocytes within oviducts), follicular development (determined by histology), and oocyte integrity were examined. The OCD were divided into 2 groups: offspring from rats with 17% and 28% of overweight (OCD17 and OCD28, respectively). Both OCD groups showed higher body weight, but OCD28 also exhibited early vaginal opening and higher ovarian weight and glycemia at euthanasia compared with OSD. Both OCD17 and OCD28 had lower number of primordial and primary follicles, and only OCD28 exhibited lower number of antral follicles, all compared with OSD rats. In addition, both OCD17 and OCD28 had higher ovulation rate than controls, and OCD28 had lower number of healthy oocytes, which, in turn, exhibited morphological alterations such as larger perivitelline space and zona pellucida than those of control animals. These results suggest that maternal overweight may severely affect the reproductive ability of the offspring, likely as a result of altering the organogenesis.

Repeated lifestyle interventions lead to progressive weight loss: A retrospective review chart study.

This study aimed to investigate whether repeated lifestyle interventions lead to progressive weight loss or to weight cycling. A retrospective review chart study with follow-up on 2120 participants (mean±SD age 36±15 years; body weight 116±28 kg; fat 43±6%). All had participated in one to four 11-12 week lifestyle interventions (residential weight loss programme, mixed activities). Weight loss was promoted through a hypocaloric diet (-500 to -700 kcal/day) and daily physical activity (1-3 hours/day). Primary outcomes were weight loss and change in body composition (bioimpedance measurements) after the intervention periods and at follow-up. A total of 2120, 526, 139 and 47 people participated in one to four interventions with mean±SEM times from start to follow-up of 1.3±0.1, 2.9±0.2, 4.2±0.3 and 5.2±0.4 years respectively. Overall 50, 41, 18 and 11% of the participants were lost to follow-up after one to four interventions, respectively. The cumulated weight loss at follow-up increased with the number of interventions from one to four: 12.2±0.1, 15.9±0.7, 16.1±1.2 and 18.5±2.0 kg ( p<0.001). The ratios between cumulated loss of fat and fat free mass after one to four interventions decreased with the number of interventions (2.4, 2.2, 2.1 and 1.4). Rates of weight loss during the interventions ranged from 0.70±0.06 to 1.06±0.01 kg/week and the maximum weight regain during the follow-up periods was 0.039±0.007 kg/week. Repeated relatively short lifestyle interventions in a selected and motivated group can be an efficient method for weight loss maintenance with only limited body weight cycling in the interim periods. However, the relationship between loss of fat and fat free mass might change in an unfavourable direction.

Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice

Dieting often leads to body weight cycling involving repeated weight loss and regain. However, little information is available regarding rapid-response serum markers of overnutrition that predict body weight alterations during weight cycling. Here, we report the rapid response of serum leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine that induces insulin resistance in skeletal muscle, during diet-induced weight cycling in mice. A switch from a high-fat diet (HFD) to a regular diet (RD) in obese mice gradually decreased body weight but rapidly decreased serum LECT2 levels within 10 days. In contrast, a switch from a RD to a HFD rapidly elevated serum LECT2 levels. Serum LECT2 levels showed a positive correlation with liver triglyceride contents but not with adipose tissue weight. This study demonstrates the rapid response of LECT2 preceding body weight alterations during weight cycling in mice and suggests that measurement of serum LECT2 may be clinically useful in the management of obesity.

Long-Term High Fat Diet Has a Profound Effect on Body Weight, Hormone Levels, and Estrous Cycle in Mice

BackgroundObesity causes several health complications along with disruption of the reproductive system. The aim of the current study was to determine how long-term intake of very high fat diet (VHFD) changes the hormonal milieu, affecting the cellular morphology and reproductive cycle in female mice.Material/MethodsMice were fed on normal diet (ND) and VHFD for 2 weeks, 12 weeks, and 25–27 weeks. We assessed changes in body weight, food consumption, energy intake, cellular and tissue morphology, hormonal levels (leptin, insulin, and estradiol), and vaginal smears were performed at various time points to determine the length and cellularity at each stage of the estrous cycle.ResultsMice fed on VHFD showed a significant increase in weight gain, reduction in food intake, and increase in energy intake compared to animals fed on ND, indicating that the caloric density of the diet is responsible for the differences in weight gain. Hormonal analysis showed hyperleptinemia, hyperinsulinemia, and increases in estrogen levels, along with increases in size of the islet of Langerhans and adipocytes. After 25–27 weeks, all animals fed on VHFD showed complete acyclicity; elongation of phases (e.g., diestrous), skipping of phases (e.g., metestrous), or a combination of both, indicating disruption in the reproductive cycle. Quantitative analysis showed that in the diestrous phase there was a 70% increase in cell count in VHFD compared to animals fed on ND.ConclusionsThe above results show that morphological and hormonal changes caused by VHFD probably act via negative feedback to the hypothalamic-pituitary axis to shut down reproduction, which has a direct effect on the estrous cycle, causing acyclicity in mice.

Effect of sloped walking on lower limb muscle forces

Lower limb joint loadings are increased during sloped walking compared to level walking and muscle forces are major contributors to lower limb joint forces. Therefore, the aim of this study was to analyze lower limb muscle forces during sloped walking at different inclinations. Eighteen healthy male participants (27.0±4.7y, 1.80±0.05m, 74.5±8.2kg) walked at a pre-set speed of 1.1m/s on a ramp at the inclinations of 0°, ±6°, ±12° and ±18°. Kinematic data were captured with a motion capture system and kinetic data were recorded with two force plates imbedded into the ramp. A musculoskeletal model was used to compute lower limb muscle forces (normalized to body weight and gait cycle duration). During downhill walking gluteus maximus, quadriceps, soleus, peroneus and tibialis anterior muscle forces increased (p≤0.002) compared to level walking, while gluteus minimus, piriformis, adductor, iliopsoas, hamstrings and gastrocnemii muscle forces decreased (p≤0.002). Uphill walking decreased gluteus minimus, iliopsoas and tibialis anterior muscle forces (p≤0.002), while all other muscle forces increased (p≤0.002, except gluteus medius). Joint-muscle-force waveforms provided information on possible muscle contributions to joint compression forces. The most important muscles were: gluteus medius for hip forces, quadriceps and gastrocnemii for tibiofemoral forces, quadriceps for patellofemoral forces and triceps surae for ankle forces. The contribution of each muscle changed with the inclination during sloped walking compared to level walking. The current study provided important information on muscle forces during sloped walking that can be useful for rehabilitation and training procedures.

The systemic and gonadal toxicity of 3-methylcholanthrene is prevented by daily administration of α-naphthoflavone.

In the present study, we investigated the effect of 3-methylcholanthrene (3MC) on sexual maturity and the ability of α-naphthoflavone (αNF) to prevent this action. To this end, immature rats were daily injected intraperitoneally with 3MC (0.1 or 1mg/kg) and/or αNF (80mg/kg). Body weight, vaginal opening and estrous cycle were recorded and ovaries were obtained on the day of estrus. Ovarian weight, ovulation rate (measured by the number of oocytes within oviducts), and follicular development (determined by histology) were studied. No differences were found in body weight, ovarian weight, day of vaginal opening, or the establishment of the estrous cycle among the different groups of rats. However, animals treated with 3MC, at both doses, exhibited a lower number of primordial, primary, preantral and antral follicles than controls. Also, 3MC inhibited the ovulation rate and induced an overexpression of both the Cyp1a1 and Cyp1b1 genes, measured by chromatin immunoprecipitation assay. The daily treatment with αNF alone increased the number of follicles in most of the stages analyzed when compared with controls. Moreover, the αNF treatment prevented completely not only the 3MC-induced decrease in all types of follicles but also the 3MC-induced overexpression of Cyp enzymes and the genetic damage in bone marrow cells and oocytes. These results suggest that (i) daily exposure to 3MC during the pubertal period destroys the follicle reserve and alters the ovulation rate; (ii) the 3MC action seems to be mediated by an aryl hydrocarbon receptor-dependent mechanism; (iii) daily administration of αNF has a clear stimulatory action on the ovarian function; and (iv) αNF may prevent both the systemic and gonadal 3MC-induced toxicity.

Effect of the Exposure to Progesterone Analogues in the Proliferation and Production of TNF‐alpha and IL‐10 by Circulating Leukocytes

Exposure to progesterone analogues is related to physiological alterations, including changes in body weight, behavior and estrous cycles. Use of these drugs for contraceptive purposes is statistically associated with the appearance of gynecologic pathologies, such as breast, uterine, ovarian and endometrial cancer. The main objective of this study was to analyze the effect of the exposure to progesterone analogues contained in oral contraceptives on the proliferation and cytokine production in circulating mononuclear leukocytes.We sampled 20 clinically healthy women who had not been previously exposed to oral contraceptives. Routine clinical data were collected and a 10 mL blood sample by venipuncture was obtained. Mononuclear leukocytes were isolated by Hypaque‐Ficoll density gradient. 1 X 106 cells were plated in 12 well plates in AIM‐V‐medium and exposed to the oral contraceptive at an equivalent dose to that found in serum (5 mg/mL), as well as a lower and higher dose (2.5 and 10 mg/mL). Cells were cultured for 3 and 24 hrs. Cell supernatants were used to measure TNF‐α and IL‐10 concentrations by ELISA and the remaining cells were harvested and used to estimate cell proliferation by propidium iodide incorporation by flow cytometry.We observed that administration of progesterone analogs from oral contraceptives increases the concentration of IL‐10 and decreases TNF‐α in cell supernatants after 24 hrs of exposure at a dose of 10 mg/mL, although the only statistical difference was observed with TNF‐α. Regarding cellular proliferation, we found that the same concentration reduced leukocyte proliferation, since we observed decreased incorporation of propidium iodide. Our preliminary data suggests that high concentrations of progesterone analogs may impair the pro‐inflammatory capacity and proliferation of mononuclear cells in circulation, and may increase the susceptibility to infection and cancer.Support or Funding InformationConsejo Mexiquense de Ciencia y Tecnología