Insulin is a hormone secreted by pancreaticβcells.The concentration of glucose in circulation is proportional to the secretion of insulin by these cells.In target cells,insulin binds to its receptors and activates ph...Insulin is a hormone secreted by pancreaticβcells.The concentration of glucose in circulation is proportional to the secretion of insulin by these cells.In target cells,insulin binds to its receptors and activates phosphatidylinositol-3-kinase/protein kinase B,inducing different mechanisms depending on the cell type.In the liver it activates the synthesis of glycogen,in adipose tissue and muscle it allows the capture of glucose,and in the hypothalamus,it regulates thermogenesis and appetite.Defects in insulin function[insulin resistance(IR)]are related to the development of neurodegenerative diseases in obese people.Furthermore,in obesity and diabetes,its role as an anorexigenic hormone in the hypothalamus is diminished during IR.Therefore,hyperphagia prevails,which aggravates hyperglycemia and IR further,becoming a vicious circle in which the patient cannot regulate their need to eat.Uncontrolled calorie intake induces an increase in reactive oxygen species,overcoming cellular antioxidant defenses(oxidative stress).Reactive oxygen species activate stress-sensitive kinases,such as c-Jun Nterminal kinase and p38 mitogen-activated protein kinase,that induce phosphorylation in serine residues in the insulin receptor,which blocks the insulin signaling pathway,continuing the mechanism of IR.The brain and pancreas are organs mainly affected by oxidative stress.The use of drugs that regulate food intake and improve glucose metabolism is the conventional therapy to improve the quality of life of these patients.Currently,the use of antioxidants that regulate oxidative stress has given good results because they reduce oxidative stress and inflammatory processes,and they also have fewer side effects than synthetic drugs.展开更多
The Src homology 2B(SH2B)family members(SH2B1,SH2B2 and SH2B3)are adaptor signaling proteins containing characteristic SH2 and PH domains.SH2B1(also called SH2-B and PSM)and SH2B2(also called APS)are able to form homo...The Src homology 2B(SH2B)family members(SH2B1,SH2B2 and SH2B3)are adaptor signaling proteins containing characteristic SH2 and PH domains.SH2B1(also called SH2-B and PSM)and SH2B2(also called APS)are able to form homo-or hetero-dimers via their N-terminal dimerization domains.Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins,including Janus kinase 2(JAK2),TrkA,insulin receptors,insulin-like growth factor-1 receptors,insulin receptor substrate-1(IRS1),and IRS2.SH2B1 enhances leptin signaling by both stimulating JAK2 activity and assembling a JAK2/IRS1/2 signaling complex.SH2B1 promotes insulin signaling by both enhancing insulin receptor catalytic activity and protecting against dephosphorylation of IRS proteins.Accordingly,genetic deletion of SH2B1 results in severe leptin resistance,insulin resistance,hyperphagia,obesity,and type 2 diabetes in mice.Neuronspecific overexpression of SH2B1βtransgenes protects against diet-induced obesity and insulin resistance.SH2B1 in pancreaticβcells promotesβcell expansion and insulin secretion to counteract insulin resistance in obesity.Moreover,numerous SH2B1 mutations are genetically linked to leptin resistance,insulin resistance,obesity,and type 2 diabetes in humans.Unlike SH2B1,SH2B2 and SH2B3 are not required for the maintenance of normal energy and glucose homeostasis.The metabolic function of the SH2B family is conserved from insects to humans.展开更多
AIM: To determine the expression levels of gastrointestinal nesfatin-1 in ventromedial hypothalamic nucleus (VMH)-lesioned (obese) and ventrolateral hypothalamic nucleus (VLH)-lesioned (lean) rats that exhibit an imba...AIM: To determine the expression levels of gastrointestinal nesfatin-1 in ventromedial hypothalamic nucleus (VMH)-lesioned (obese) and ventrolateral hypothalamic nucleus (VLH)-lesioned (lean) rats that exhibit an imbalance in their energy metabolism and gastric mobility.展开更多
We investigated the growth and body composition of Nile tilapia under five different feeding regimes. A control group was fed to satiation twice daily for 185 days; four treatment groups were fed at intervals of 2, 3,...We investigated the growth and body composition of Nile tilapia under five different feeding regimes. A control group was fed to satiation twice daily for 185 days; four treatment groups were fed at intervals of 2, 3, 4 or 7 days(dietary ‘restricted' period, days 0–80) and then fed to satiation(‘refeeding' period, days 80–185). Compensatory growth in weight and length of the feed-restricted groups was observed during the refeeding period. However, the growth of none of the restricted groups caught up with that of the control group over the experimental period. Feed intake upon refeeding increased with the duration of deprivation. There were no significant differences in feed efficiency between the restricted and control groups during the refeeding stage, suggesting that hyperphagia was the mechanism responsible for the increased growth rates during this period. Tilapia preferentially used n-3 polyunsaturated fatty acids and nonessential amino acids during the restricted-feeding period. Higher production was achieved by higher feed consumption. We suggest that if attainment of market size in minimum time is required, fish should be consistently fed to satiation, while taking care to avoid the possible negative consequences of overfeeding.展开更多
Background: Several rodent models are available to study obesity and obesity associated diabetic problems. We developed an obese mutant rat model viz., WNIN/GR-Ob from our existing WNIN (Inbred Wistar) stock of rats, ...Background: Several rodent models are available to study obesity and obesity associated diabetic problems. We developed an obese mutant rat model viz., WNIN/GR-Ob from our existing WNIN (Inbred Wistar) stock of rats, which exhibit hyperglycemia on challenge with oral glucose. Since such impaired glucose tolerance (IGT) is a fore runner to frank diabetes status, we carried out a study to challenge the animals with different purified carbohydrate sources (glucose, sucrose, starch) and see the outcome. Methods: 48 obese rats of both genders and equal number of lean littermates of 35 days of age were taken for the study and were divided in to four groups, A, B, C, and D. A group received purified glucose based diet, B, received purified sucrose, C, received purified starch and the D, served as the control, receiving standard laboratory rat chow developed at our centre, containing roasted bengal gram as the source of carbohydrate. All diets were isocaloric in nature and contained 56 % carbohydrate in principle. Animals were fed for 8 weeks and parameters like food intake, body weights, and plasma glucose and insulin levels were measured in experimental and control rats at initial, 4 weeks and 8 weeks. Results: As expected, food intake, body weight and feed efficiency ratio were significantly higher in obese rats of all groups as compared to their lean littermate controls and also higher in stock diet, compared to purified diets. Both lean and obese animals showed higher values of glucose and insulin on purified diets compared to control diet. But amongst lean and obese animals, the latter showed sexual dimorphism in their response, the situation being worse in starch fed (C) group. Amongst the obese animals, the males seem to suffer more, compared to females, in starch fed group, followed by glucose and sucrose fed in that order. Conclusions: WNIN/ GR-Ob rats thus seem to be a useful animal model, vulnerable to diet manipulations, especially to carbohydrates. This has the potential to be used as a diabetic model, more akin to human systems, where diet is the major trigger for precipitating diabetes.展开更多
The imminent danger of the Covid-19 pandemic has accelerated research in pharmaceuticals that either target the viral Spike proteins fusion with ACE2 receptors,or the infectious RNA replication that often overwhelms i...The imminent danger of the Covid-19 pandemic has accelerated research in pharmaceuticals that either target the viral Spike proteins fusion with ACE2 receptors,or the infectious RNA replication that often overwhelms immune defences.The scope of this review was to elucidate the main human vulnerabilities to Covid-19,including the accumulation of ACE2 receptors in testes,adipose tissue,thyroid,heart and kidneys that escalate viral affinity in males,the aged,and certain medical conditions,including diabetes,CVD,and pulmonary diseases.Pre-existing inflammation inherent in obesity may exacerbate the“cytokine storm,”a rampaging immune reaction during the course of Covid-19 that is deleterious to the host.We examined the molecular dynamics illustrating the action of new therapeutics necessary for Covid-19 patients;the estradiol advantage hypothesis;alternative therapies including hormone replacement procedures and mesenchymal stem cells;plus preventive and protective interventions.The current perspective also explored the primary components of dysregulated health predisposing individuals to Covid-19,including hormonal imbalance,increased lipids and lipoproteins,thyroid dysfunction,degraded fitness,and age-related testosterone decline accompanied by cortisol increase that provokes stress eating behaviours and weight accumulation.Obesity increases the probability of Covid-19 infection due to its abundance of ACE2 receptors;while physical activity may decrease Covid-19 vulnerability,by reducing fat and increasing muscle mass that manifests a relatively inhibited ACE2 expression.Several weight management solutions feature lasers and radiofrequency which diminish subcutaneous adiposity but do not enhance fitness.A data metanalysis of seven recently published clinical studies on 95 obese individuals,73 males and 22 females with an average BMI of 30.9,demonstrated visceral fat reduction combined with increased skeletal muscle mass.It also revealed a statistically significant decrease in BMI,lipids,lipoproteins,inflammation and toxicity as measured by CRP,Creatinine and Bilirubin respectively,juxtaposed by optimally healthier levels of Cortisol,Testosterone,Free T3,IGF-1,Insulin,and the appetite controlling hormones Leptin and Ghrelin.展开更多
Thyroid hormone excess secondary to global type 3 deiodinase(DIO3)deficiency leads to increased locomotor activity and reduced adiposity,but also to concurrent alterations in parameters of the leptin-melanocortin syst...Thyroid hormone excess secondary to global type 3 deiodinase(DIO3)deficiency leads to increased locomotor activity and reduced adiposity,but also to concurrent alterations in parameters of the leptin-melanocortin system that would predict obesity.To distinguish the underlying contributions to the energy balance phenotype of Dlo3 deficiency,we generated mice with thyroid hormone excess targeted to pro-opiomelanocortin(POMC)-expressing cells via cell-specific DIO3 inactivation.These mice exhibit a male-specific phenotype of reduced hypothalamic Pomc expression,hyperphagia,and increased activity in brown adipose tissue,with adiposity and serum levels of leptin and thyroid hormones remained normal.These male mice also manifest a marked and widespread hypothalamic reduction in the expression of bone morphogenetic receptor 1a(BMPR1A),which has been shown to cause similar phenotypes when inactivated in PoMC-expressing cells.Our results indicate that developmental overexposure to thyroid hormone in PoMC-expressing cells programs energy balance mechanisms in a sexually dimorphic manner by suppressing adult hypothalamic BMPR1A expression.展开更多
文摘Insulin is a hormone secreted by pancreaticβcells.The concentration of glucose in circulation is proportional to the secretion of insulin by these cells.In target cells,insulin binds to its receptors and activates phosphatidylinositol-3-kinase/protein kinase B,inducing different mechanisms depending on the cell type.In the liver it activates the synthesis of glycogen,in adipose tissue and muscle it allows the capture of glucose,and in the hypothalamus,it regulates thermogenesis and appetite.Defects in insulin function[insulin resistance(IR)]are related to the development of neurodegenerative diseases in obese people.Furthermore,in obesity and diabetes,its role as an anorexigenic hormone in the hypothalamus is diminished during IR.Therefore,hyperphagia prevails,which aggravates hyperglycemia and IR further,becoming a vicious circle in which the patient cannot regulate their need to eat.Uncontrolled calorie intake induces an increase in reactive oxygen species,overcoming cellular antioxidant defenses(oxidative stress).Reactive oxygen species activate stress-sensitive kinases,such as c-Jun Nterminal kinase and p38 mitogen-activated protein kinase,that induce phosphorylation in serine residues in the insulin receptor,which blocks the insulin signaling pathway,continuing the mechanism of IR.The brain and pancreas are organs mainly affected by oxidative stress.The use of drugs that regulate food intake and improve glucose metabolism is the conventional therapy to improve the quality of life of these patients.Currently,the use of antioxidants that regulate oxidative stress has given good results because they reduce oxidative stress and inflammatory processes,and they also have fewer side effects than synthetic drugs.
文摘The Src homology 2B(SH2B)family members(SH2B1,SH2B2 and SH2B3)are adaptor signaling proteins containing characteristic SH2 and PH domains.SH2B1(also called SH2-B and PSM)and SH2B2(also called APS)are able to form homo-or hetero-dimers via their N-terminal dimerization domains.Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins,including Janus kinase 2(JAK2),TrkA,insulin receptors,insulin-like growth factor-1 receptors,insulin receptor substrate-1(IRS1),and IRS2.SH2B1 enhances leptin signaling by both stimulating JAK2 activity and assembling a JAK2/IRS1/2 signaling complex.SH2B1 promotes insulin signaling by both enhancing insulin receptor catalytic activity and protecting against dephosphorylation of IRS proteins.Accordingly,genetic deletion of SH2B1 results in severe leptin resistance,insulin resistance,hyperphagia,obesity,and type 2 diabetes in mice.Neuronspecific overexpression of SH2B1βtransgenes protects against diet-induced obesity and insulin resistance.SH2B1 in pancreaticβcells promotesβcell expansion and insulin secretion to counteract insulin resistance in obesity.Moreover,numerous SH2B1 mutations are genetically linked to leptin resistance,insulin resistance,obesity,and type 2 diabetes in humans.Unlike SH2B1,SH2B2 and SH2B3 are not required for the maintenance of normal energy and glucose homeostasis.The metabolic function of the SH2B family is conserved from insects to humans.
基金Supported by Grants from National Natural Science Foundation of China,No.81070305the Natural Science Foundation of Shandong Province,No.zr2010hm066
文摘AIM: To determine the expression levels of gastrointestinal nesfatin-1 in ventromedial hypothalamic nucleus (VMH)-lesioned (obese) and ventrolateral hypothalamic nucleus (VLH)-lesioned (lean) rats that exhibit an imbalance in their energy metabolism and gastric mobility.
文摘We investigated the growth and body composition of Nile tilapia under five different feeding regimes. A control group was fed to satiation twice daily for 185 days; four treatment groups were fed at intervals of 2, 3, 4 or 7 days(dietary ‘restricted' period, days 0–80) and then fed to satiation(‘refeeding' period, days 80–185). Compensatory growth in weight and length of the feed-restricted groups was observed during the refeeding period. However, the growth of none of the restricted groups caught up with that of the control group over the experimental period. Feed intake upon refeeding increased with the duration of deprivation. There were no significant differences in feed efficiency between the restricted and control groups during the refeeding stage, suggesting that hyperphagia was the mechanism responsible for the increased growth rates during this period. Tilapia preferentially used n-3 polyunsaturated fatty acids and nonessential amino acids during the restricted-feeding period. Higher production was achieved by higher feed consumption. We suggest that if attainment of market size in minimum time is required, fish should be consistently fed to satiation, while taking care to avoid the possible negative consequences of overfeeding.
文摘Background: Several rodent models are available to study obesity and obesity associated diabetic problems. We developed an obese mutant rat model viz., WNIN/GR-Ob from our existing WNIN (Inbred Wistar) stock of rats, which exhibit hyperglycemia on challenge with oral glucose. Since such impaired glucose tolerance (IGT) is a fore runner to frank diabetes status, we carried out a study to challenge the animals with different purified carbohydrate sources (glucose, sucrose, starch) and see the outcome. Methods: 48 obese rats of both genders and equal number of lean littermates of 35 days of age were taken for the study and were divided in to four groups, A, B, C, and D. A group received purified glucose based diet, B, received purified sucrose, C, received purified starch and the D, served as the control, receiving standard laboratory rat chow developed at our centre, containing roasted bengal gram as the source of carbohydrate. All diets were isocaloric in nature and contained 56 % carbohydrate in principle. Animals were fed for 8 weeks and parameters like food intake, body weights, and plasma glucose and insulin levels were measured in experimental and control rats at initial, 4 weeks and 8 weeks. Results: As expected, food intake, body weight and feed efficiency ratio were significantly higher in obese rats of all groups as compared to their lean littermate controls and also higher in stock diet, compared to purified diets. Both lean and obese animals showed higher values of glucose and insulin on purified diets compared to control diet. But amongst lean and obese animals, the latter showed sexual dimorphism in their response, the situation being worse in starch fed (C) group. Amongst the obese animals, the males seem to suffer more, compared to females, in starch fed group, followed by glucose and sucrose fed in that order. Conclusions: WNIN/ GR-Ob rats thus seem to be a useful animal model, vulnerable to diet manipulations, especially to carbohydrates. This has the potential to be used as a diabetic model, more akin to human systems, where diet is the major trigger for precipitating diabetes.
文摘The imminent danger of the Covid-19 pandemic has accelerated research in pharmaceuticals that either target the viral Spike proteins fusion with ACE2 receptors,or the infectious RNA replication that often overwhelms immune defences.The scope of this review was to elucidate the main human vulnerabilities to Covid-19,including the accumulation of ACE2 receptors in testes,adipose tissue,thyroid,heart and kidneys that escalate viral affinity in males,the aged,and certain medical conditions,including diabetes,CVD,and pulmonary diseases.Pre-existing inflammation inherent in obesity may exacerbate the“cytokine storm,”a rampaging immune reaction during the course of Covid-19 that is deleterious to the host.We examined the molecular dynamics illustrating the action of new therapeutics necessary for Covid-19 patients;the estradiol advantage hypothesis;alternative therapies including hormone replacement procedures and mesenchymal stem cells;plus preventive and protective interventions.The current perspective also explored the primary components of dysregulated health predisposing individuals to Covid-19,including hormonal imbalance,increased lipids and lipoproteins,thyroid dysfunction,degraded fitness,and age-related testosterone decline accompanied by cortisol increase that provokes stress eating behaviours and weight accumulation.Obesity increases the probability of Covid-19 infection due to its abundance of ACE2 receptors;while physical activity may decrease Covid-19 vulnerability,by reducing fat and increasing muscle mass that manifests a relatively inhibited ACE2 expression.Several weight management solutions feature lasers and radiofrequency which diminish subcutaneous adiposity but do not enhance fitness.A data metanalysis of seven recently published clinical studies on 95 obese individuals,73 males and 22 females with an average BMI of 30.9,demonstrated visceral fat reduction combined with increased skeletal muscle mass.It also revealed a statistically significant decrease in BMI,lipids,lipoproteins,inflammation and toxicity as measured by CRP,Creatinine and Bilirubin respectively,juxtaposed by optimally healthier levels of Cortisol,Testosterone,Free T3,IGF-1,Insulin,and the appetite controlling hormones Leptin and Ghrelin.
基金We are grateful for the technical support of the Molecular Phenotyping,Histopathology and Histomorphometry,Confocal Microscopy,and Physiology Core facilities at MaineHealth Institute for Research.These core facilities are supported by grants P30GM106391,U54GM115516,and P20GM121301 from the National Institute of General Medical SciencesThis work was supported by grant DK095908(to A.H.)from the National Institute of Diabetes,Digestive and Kidney Diseases,National Institutes of Health,USA.
文摘Thyroid hormone excess secondary to global type 3 deiodinase(DIO3)deficiency leads to increased locomotor activity and reduced adiposity,but also to concurrent alterations in parameters of the leptin-melanocortin system that would predict obesity.To distinguish the underlying contributions to the energy balance phenotype of Dlo3 deficiency,we generated mice with thyroid hormone excess targeted to pro-opiomelanocortin(POMC)-expressing cells via cell-specific DIO3 inactivation.These mice exhibit a male-specific phenotype of reduced hypothalamic Pomc expression,hyperphagia,and increased activity in brown adipose tissue,with adiposity and serum levels of leptin and thyroid hormones remained normal.These male mice also manifest a marked and widespread hypothalamic reduction in the expression of bone morphogenetic receptor 1a(BMPR1A),which has been shown to cause similar phenotypes when inactivated in PoMC-expressing cells.Our results indicate that developmental overexposure to thyroid hormone in PoMC-expressing cells programs energy balance mechanisms in a sexually dimorphic manner by suppressing adult hypothalamic BMPR1A expression.
