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Objective:To analyze nine cases of pregnancy and lactation-associated osteoporosis(PLO) along with a literature review to improve clinicians′ knowledge of the disease.Methods:We collected medical history, laboratory examination, bone mineral density(BMD) scan, treatment and follow-up data of 9 inpatients with PLO in the Endocrinology Department of the First Affiliated Hospital of Zhengzhou University from January 2014 to June 2021.Results:The median age of onset of 9 patients with PLO was 30 years(22-37 years). All 9 patients presented low back pain, and the median time of low back pain after childbirth was 2.5 months(0.5-7 months). 89% of the patients presented vertebral compression fractures, and the mean number of vertebral fractures was 4.6. Eight patients with PLO showed osteoporosis by dual X-ray absorpiometry(DXA) scan, and one patient showed bone loss by quantitative CT scan. Osteoporosis predominated in the trabecular bone. After the diagnosis, nine patients with PLO stopped breastfeeding and were given calcium and vitamin D preparations. Seven patients were given bisphosphonates and one patient was treated with teriparatide followed by denosumab. The back pain of all patients was relieved, with the median of relief time being 3 months(7 d-6 m). After treatment initiation, BMD was increased in eight patients, especially obvious in the lumbar spine. No new clinical fractures occurred during the follow-up.Conclusions:For women with low back pain and shortened height in late pregnancy or breastfeeding, the possibility of PLO should be considered. Prompt diagnosis and early medical interventions are of utmost importance to reduce the risk of subsequent fractures and improve the prognosis.
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Objective:To observe the effect of shift work on the stability of the circadian clock and insulin sensitivity in non-overweight/obese individuals with normal blood glucose, and explore underlying connection.Methods:Female shift working nurses in the Department of Blood Transplantation and non-shift working nurses in the Health Management Center in the First Affiliated Hospital of Zhengzhou University were divided into shift worker group (SW group) and non-shift worker group (NSW group). Serum inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α)], adipokines (adiponectin, leptin, chemerin, visfatin), and melatonin levels were measured using enzyme linked immunosorbent assay (ELISA). Realtime fluorescence quantitative PCR was performed to detect peripheral blood circadian clock genes circadian locomotor output cycles protein kaput(Clock) and brain and muscle ARNT-like protein 1(Bmal1). Cortisol and fasting insulin were measured by chemiluminescent microparticle immunoassay, and HbA 1C was measured by capillary electrophoresis. In addition, visceral fat area (VFA) was assessed with bioelectrical impedance analyzer, and mid-sleep time composite phase deviations (CPD) was calculated based on the International Physical Activity Short Questionnaire. Results:SW group had lower serum level of melatonin ( P=0.023) and higher cortisol ( P=0.001) than the NSW group, and altered mRNA expression of Clock and Bmal1 ( P=0.034, P=0.047). Fasting blood glucose and HbA 1C in the SW group, although in the normal range, had been higher than in the NSW group ( P=0.011, P=0.033). Although body mass index was normal in SW group, VFA had been higher than that of the NSW group ( P=0.010). And homeostasis model assessment for insulin resistance (HOMA-IR), IL-6, TNF-α, leptin, chemerin, and visfatin were significantly higher in the SW group than NSW group ( P=0.033, P=0.012, P=0.001, P=0.011, P=0.021, P=0.007). In addition, adjusting for body mass index and activity factors revealed a significant positive correlation between CPD and VFA ( r=0.434, P=0.049), inflammatory factors IL-6 ( r=0.514, P=0.017) and TNF-α ( r=0.700, P<0.001) and pro-inflammatory adipokines leptin ( r=0.473, P=0.030), chemerin ( r=0.439, P=0.047), visfatin ( r=0.521, P=0.015). Conclusion:Shift work can affect circadian clock, with increased visceral adiposity, pro-inflammatory adipokines, inflammatory factors and decreased insulin sensitivity in women without overweight/obese.
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Objective:To observe the effects of continuous light exposure on skeletal muscle fiber type transformation and lipid metabolism, and to explore its internal relationship.Methods:Mice were randomly divided into normal light group and 24-hour continuous light group by random number table. The serum and skeletal muscle lipid content and urine 6-sulfatoxymelatonin(6-SML)level were detected by ELISA. The expression of circadian clock and lipid metabolism related genes mRNA were observed by realtime PCR. The muscle fiber type and lipid deposition were evaluated by tissue immunofluorescence as well as oil red O staining.Results:Compared with the normal light group, the level of 6-SML in urine at night decreased( P<0.05), and the expression level and rhythm of brain and muscle ARNT-like protein 1(Bmal1), circadian locomotor output cycles protein kaput(Clock), and period 2(Per2)mRNA in the skeletal muscle changed in continuous light group. In addition, the body weight, blood lipid, free fatty acid, and triglyceride contents of skeletal muscle in continuous light group increased significantly( P<0.05 or P<0.01), the expression of carnitine palmitoyltransferase 1b (Cpt1b)mRNA, the key enzyme of fatty acid oxidation, decreased significantly( P<0.05), while the expression of stearoyl-CoA desaturase(Scd1)mRNA, a lipid synthesis related gene, increased significantly( P<0.01). Further immunofluorescence analysis showed that the proportion of slow muscle fibers decreased and that of fast muscle fibers increased in continuous light group(both P<0.05). Conclusion:The process of ectopic deposition of lipid in skeletal muscle in mice induced by continuous light exposure may be related to the remodeling of skeletal muscle fibers.
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OBJECTIVE@#To explore the genetic basis for an infant with neonatal diabetes (NDM) and multiple malformations.@*METHODS@#Genetic variants were detected by next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing.@*RESULTS@#A de novo heterozygous variant, c.1454_1455del(p.K485Rfs), was detected in exon 5 of the GATA6 gene. The variant was undetected in his parents and unreported previously. Bioinformatic analysis predicted the variant to be pathogenic.@*CONCLUSION@#The heterozygous variant of c.1454_1455del(p.K485Rfs) of the GATA6 gene probably underlies the disease in this child. Genetic testing can facilitate diagnosis and genetic counseling for NDM.
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Adult , Female , Humans , Infant, Newborn , Male , Abnormalities, Multiple , Diabetes Mellitus/genetics , Genetic Testing , Heterozygote , High-Throughput Nucleotide Sequencing , Sequence Deletion/geneticsABSTRACT
As a pandemic metabolic disease, obesity has become a worldwide problem, which endangering human health. The change in body weight reflects the energy imbalance. And the homeostasis regulation of the central and peripheral melanocortin system may maintain the energy balance and then affect the body weight. Recent studies have found that melanocortin receptor-4 ( MC4R) plays an important role in energy homeostasis and body weight changes, but its specific mechanism needs further elucidation. In this paper, we reviewed the research progress of MC4R in body weight and energy regulation, so as to provide a theoretical basis for further exploring the potential role of MC4R in improving energy metabolism imbalance and obesity.
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Objective To establish a stable and reliable mouse model as an alternative to the traditional model of impaired glucose tolerance induced by calorie restriction and its effect on glucose homeostasis.Methods Forty 16-week-old SPF C57BL/6J mice (half male and half female) were randomly divided into four groups by sex and the way of feeding.The mice in the ad libitum (AL) group had free access to basic diet, while the mice in the intermittent fasting (IF) group had normal diet and fasting on alternate days, with free access to water on the fasting days.The changes of body weight and blood glucose concentration in each group were monitored, and intraperitoneal glucose tolerance test and insulin tolerance test in mice were performed before and after the 12-week IF treatment.Results At 12 weeks after IF treatment, the body weight and blood glucose concentration of mice did not show significant difference.After i.p.injection of glucose, the blood glucose concentration of IF mice was less increased than the AL group, and after the insulin injection, the blood glucose concentration was more decreased.Compared to the AL group, the areas under the curve of tolerance test in the IF group were significantly decreased (P < 0.05).Conclusions After IF treatment, the mice show an enhanced sensitivity to insulin and improved glucose tolerance.This establishment method of mouse model of intermittent fasting is easy and simple, therefore, can be used as an effective alternative to traditional calorie restriction model of impaired glucose tolerance.
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[Summary] In this study, PubMed, Embase, China National Knowledge Infrastructure, databases VIP Chinese Periodical Database, and Wanfang Chinese Periodical Database were systematically searched for the case-control study related β3-adrenergic receptor ( ADRB3 ) Trp64Arg gene polymorphism to overweight/obesity among children from 1962 to 2014.Twelve eligible studies with 2 222 overweight/obese children and 1 955 normal children were included according the uniform inclusion and exclusion criteria.Meta-analyses showed that Trp64Arg polymorphism was associated with significantly increased overweight/obesity risk in Arg carriers among children( OR=1.34,95%CI1.17-1.53).Afterstratificationforethnicity,highlysignificantcoorelationofTrp64Argpolymorphism to overweight/obesity in Asian children(OR=1.44, 95%CI 1.23-1.68) but not significant in Europe(OR=1.05, 95%CI 0.79-1.40).It suggested that Trp64Arg polymorphism is associated with overweight/obesity susceptibility in children.Our results support an strong association between Trp64Arg polymorphism and overweight/obesity among the Asian children investigated.
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ObjectiveTo observe the effect of resveratrol on the oxidative stress and antioxidant levels of different mitochondrial subpopulations in the skeletal muscle and insulin sensitivity of rats fed with high-fat diet.MethodsMale SD rats,aged 8 weeks,were divided into normal chow (NC) group,high-fat diet(HF) group,high-fat diet plus resveratrol ( HFR ) group.After intervention for 8 weeks,the impacts of resveratrol on oxidative stress levels and antioxidant enzymes activities in subsarcolemmal ( SS ) and intermyofibrillar ( IMF ) mitochondria from skeletal muscle as well as general and skeletal mascle insulin sensitivity were assessed.ResultsCompared with NC group, insulin sensitivity was significantly reduced while reactiveoxygenspecies (ROS)and malondialdehyde(MDA) levels in SS and IMF mitochondria increased in HF group ( all P＜0.01 ).In addition,antioxidant enzyme activities were significantly decreased in SS mitochondrial and increased in IMF mitochondrial ( both P ＜ 0.05 ).Compared with HF group,the insulin sensitivity in HFR group was significantly improved.Moreover,the activities of antioxidant enzymes in SS and IMF mitochondrial were increased,and the oxidative stress levels returned to normal ( P ＜ 0.05 ).ConclusionResveratrol notably improves the oxidative stress of different skeletal muscle mitochondrial subpopulations and insulin resistance in rats fed with high-fat diet.
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ObjectiveTo investigate the effects of adult catch-up growth on insulin sensitivity and stress in rats, as well as the probable mechanism of insulin resistance. MethodsMale Sprague-Dawley rats were divided into 6 groups:caloric restriction group ( R4, caloric restriction for 4 weeks) and normal controls for 4 weeks ( NC4 ) ; catchup growth group refed with normal chow( RN4, refeeding for 4 weeks after caloric restriction for 4 weeks), catch-up growth group refed with high-fat diet( RH4, refeeding for 4 weeks after caloric restriction for 4 weeks ), normal chow (NC8) or high-fat diet( HF8 ) controls for 8 weeks. The animal model of catch-up growth was devoloped by way of refeeding after caloric restriction as scheduled. The glucose infusion rate( GIR ), 2-deoxyglucose uptake and insulinsitmulated insulin signaling in skeletal muscle during hyperinsulinemic-euglycemic clamp, plasma corticosterone, and 11β-hydroxysteroid dehydrogenase type 1 ( 11β-HSD1 ) mRNA expression level in skeletal muscle were determined.ResultsAfter caloric restriction for 4 weeks, plasma corticosterone and 1 1 β-HSD1 mRNA expression in skeletal muscle were significantly higher in R4 group compared with NC4 group( both P＜0. 05 ), but there were no differences in 2-deoxyglucose uptake and Ser473 phosphorylation of Akt in skeletal muscle between two groups. The plasma corticosterone and 11β-HSD1 mRNA expression in skeletal muscle in RN4 group were significantly higher than those in NC8 group, and were higher in RH4 group than those in NC8 and HF8 groups; while the 2-deoxyglucose uptake and insulin-stimulated Ser473 phosphorylation of Akt in skeletal muscle during the clamp in RN4 were remarkably lower than those in NC8 group, and were lower in RH4 than those in NC8, HF8, and RN4 groups (all P ＜ 0. 05 ).ConctusionsCatch-up growth rats refed with normal chow or high-fat diet are characterized by significant insulin resistance and stress in the whole body and skeletal muscle. These changes are more evident in catch-up growth rats refed with high-fat diet. The interaction of increased stress and diet might be of utmost importance in the etiology of insulin resistance in catch-up growth animals.
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dation, transiently inercasod food efficiency,and a faster growth rate of visceral adipose tissue versus body weight after nutritional rehabilitation. These findings are consistent with the characteristics of human catch-up growth.