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Background: Individuals with a phenotype of early-onset severe obesity associated with intellectual disability can have molecular diagnoses ranging from monogenic to complex genetic traits. Severe overweight is the major sign of a syndromic physical appearance and predicting the influence of a single gene and/or polygenic risk profile is extremely complicated among the majority of the cases. At present, considering rare monogenic bases as the principal etiology for the majority of obesity cases associated with intellectual disability is scientifically poor. The diversity of the molecular bases responsible for the two entities makes the appliance of the current routinely powerful genomics diagnostic tools essential. Objective: Clinical investigation of these difficult-to-diagnose patients requires pediatricians and neurologists to use optimized descriptions of signs and symptoms to improve genotype correlations. Methods: The use of modern integrated bioinformatics strategies which are conducted by experienced multidisciplinary clinical teams. Evaluation of the phenotype of the patient's family is also of importance. Results: The next step involves discarding the monogenic canonical obesity syndromes and considering infrequent unique molecular cases, and/or then polygenic bases. Adequate management of the application of the new technique and its diagnostic phases is essential for achieving good cost/efficiency balances. Conclusion: With the current clinical management, it is necessary to consider the potential coincidence of risk mutations for obesity in patients with genetic alterations that induce intellectual disability. In this review, we describe an updated algorithm for the molecular characterization and diagnosis of patients with a syndromic obesity phenotype.
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The relationship between serum Mg and blood cell counts in Chinese adult diabetes or central obesity was assessed by investigating 8163 subjects with China Health and Nutrition Survey (mean age 59â 6 years, 54â 9 % men). Participants were classified according to blood Mg (below 0â 65 mmol/l, or 0â 66-0â 94 mmol/l or above 0â 95 mmol/l), type 2 diabetes (yes/no) and central obesity (yes/no). Leucocytes, erythrocytes, platelets (PLT), Hb and glycated Hb (HbA1c) were determined using standardised methods and conditions. HbAc1, leucocytes and PLT were significantly higher among subjects with central obesity than without central obesity (P < 0â 05). A significant increase for Hb, erythrocytes, PLT, but not leucocytes, across progressive Mg groups was observed in subjects without diabetes (P < 0â 05). Hb, erythrocytes and HbAc1 were significantly higher among subjects with higher Mg than in subjects with lower Mg with diabetes (P < 0â 05). Central obesity disturbed the positive association between PLT count and serum Mg. Type 2 diabetes caused metabolism disorder in serum Mg, blood sugar and blood cell count. Hb, erythrocytes and PLT, but not leucocytes, are positively correlated with serum Mg, but this association is somehow disturbed by type 2 diabetes or central obesity.
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Plaquetas , Diabetes Mellitus Tipo 2/sangre , Eritrocitos , Leucocitos , Magnesio/sangre , Obesidad Abdominal/sangre , Anciano , Recuento de Células Sanguíneas , China , Estudios Transversales , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Encuestas NutricionalesRESUMEN
Most patients with GNB1 encephalopathy have developmental delay and/or intellectual disability, brain anomalies and seizures. Recently, two cases with GNB1 encephalopathy caused by haploinsufficiency have been reported that also show a Prader-Willi-like phenotype of childhood hypotonia and severe obesity. Here we present three new cases from our expert centre for genetic obesity in which GNB1 truncating and splice variants, probably leading to haploinsufficiency, were identified. They all have obesity, hyperphagia and intellectual deficit. The clinical cases and their weight courses are presented, together with a review of all 68 published cases with GNB1 encephalopathy. Information on weight was not mentioned in most of these articles, so we contacted authors for additional clinical information on weight status and hyperphagia. Of the 42 patients whose weight status we could determine, obesity was present in 8 patients (19%). Obesity is significantly over-represented in the group with truncating and splicing variants. In this group, we see an obesity prevalence of 75%. Since GNB1 has been linked to several key genes in the hypothalamic leptin-melanocortin pathway, which regulates satiety and energy expenditure, our data support the potential association between GNB1 haploinsufficiency and genetic obesity. We also suggest GNB1 is a candidate gene for the known obesity phenotype of the 1p36 microdeletion syndrome given this chromosomal region includes the GNB1 gene. Knowledge of an additional obesity phenotype is important for prognosis, early interventions against obesity and awareness when prescribing weight-inducing medication.
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Subunidades beta de la Proteína de Unión al GTP , Haploinsuficiencia , Obesidad , Humanos , Masculino , Femenino , Subunidades beta de la Proteína de Unión al GTP/genética , Obesidad/genética , Niño , Discapacidad Intelectual/genética , Preescolar , Fenotipo , Adolescente , Hiperfagia/genética , AdultoRESUMEN
BACKGROUND AND AIMS: Metabolic syndrome is a multifactorial pathophysiological process with complicated homeostatic disorders that arise from various systematic metabolic defects. Various theories underlie the development of metabolic syndrome but are fully not understood. METHODS: Revising PubMed and Scopus literature data on metabolic syndrome pathogenesis and management. RESULTS: The most accepted hypothesis is that a cluster of risk factors combined to obtain a truly metabolic syndrome. The pathophysiology of the metabolic syndrome depends on the underlying development path due to insulin resistance or chronic inflammation and is usually combined with neurohormonal disturbance. Meanwhile, these defects can be inherited via loss of function of certain genes that lead to severe obesity, early diabetes, or severe insulin resistance (with or without lipodystrophy). Chronic inflammation is also a driver of metabolic syndrome. Lifestyle is still the therapy of choice in managing metabolic syndrome, but unfortunately, during the lockdown, most people could not reserve a healthy regime; therefore, it can also be referred to as a pandemic with COVID-19. CONCLUSIONS: This powerful illustration shows how defects in specific encoded proteins located predominantly in the brain, pancreatic beta-cell, muscle, or fat give rise to these distinct components of the metabolic syndrome. Primarily, obesity and its sequela are the initiators of metabolic syndrome. The presence of metabolic syndrome increases the risk and severity of other pathologies' emergence, even in non-related metabolic syndrome diseases such as COVID-19. The article provides new insights into the pathogeneses and management of the metabolic syndrome.
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COVID-19 , Resistencia a la Insulina , Síndrome Metabólico , Humanos , Síndrome Metabólico/terapia , Síndrome Metabólico/complicaciones , Resistencia a la Insulina/fisiología , COVID-19/complicaciones , Control de Enfermedades Transmisibles , Obesidad/complicaciones , Obesidad/metabolismo , Inflamación/complicacionesRESUMEN
Accumulating evidence to date suggests that brown rice is superior to white rice in regard to its beneficial impact on a number of risk factors of the metabolic syndrome (MetS). However, little is known about the influence of fermented brown rice beverage on the gut microbiota in humans. We therefore hypothesized that its impact would beneficially alter the gut microbiota composition of patients with MetS. Using a 4-week randomized, single-arm study design, subjects (n = 40) were advised to consume a daily fermented brown rice beverage (BA) or fermented white rice beverage (WA) as a replacement of their main meal. Clinical and anthropometric measurements as well as fecal samples were collected at baseline and immediately after completion of the intervention. Gut microbiota was analyzed using 16S ribosomal RNA sequencing and capillary electrophoresis-time-of-flight mass spectrometry was used to measure plasma short-chain fatty acids. Interestingly, ingestion of BA in contrast to WA resulted in a unique elevation in the abundance of number of beneficial species belonging to the Clostridia class, associated with reduced inflammation, and increased short-chain fatty acid production: Lactobacillales bacterium DJF B280 (P = .005), Butyrate producing bacterium A2 207 (P = .012), and Firmicutes bacterium DJF VP44 (P = .038). This study demonstrates that consumption of BA is effective to beneficially modulate the gut microbiota compared with WA in patients with MetS.
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Microbioma Gastrointestinal , Síndrome Metabólico , Oryza , Bebidas/análisis , Ácidos Grasos Volátiles/metabolismo , Heces/microbiología , Humanos , Oryza/genética , Oryza/metabolismo , ARN Ribosómico 16S/análisisRESUMEN
This article aims to provide guidance on prevention and treatment of COVID-19 in patients with genetic obesity. Key principals of the management of patients with genetic obesity during COVID-19 pandemic for patients that have contracted COVID-19 are to be aware of: possible adrenal insufficiency (e.g., POMC deficiency, PWS); a more severe course in patients with concomitant immunodeficiency (e.g., LEP and LEPR deficiency), although defective leptin signalling could also be protective against the pro-inflammatory phenotype of COVID-19; disease severity being masked by insufficient awareness of symptoms in syndromic obesity patients with intellectual deficit (in particular PWS); to adjust medication dose to increased body size, preferably use dosing in m2; the high risk of malnutrition in patients with Sars-Cov2 infection, even in case of obesity. Key principals of the obesity management during the pandemic are to strive for optimal obesity management and a healthy lifestyle within the possibilities of the regulations to prevent weight (re)gain and to address anxiety within consultations, since prevalence of anxiety for COVID-19 is underestimated.
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COVID-19 , Manejo de la Enfermedad , Obesidad/terapia , Pandemias , Ansiedad , Estilo de Vida Saludable , Humanos , Obesidad/epidemiología , Obesidad/genéticaRESUMEN
BACKGROUND: The MEHMO (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity) syndrome, which is caused by a hemizygous variant in the EIF2S3 gene on chromosome Xp22, is associated with significant morbidity and mortality. Refractory epileptic seizures and glucose dysregulation are characteristic manifestations of the MEHMO syndrome, which can often diminish patients' quality of life. CASE: A 5-year-old boy was referred to our hospital because of profound intellectual disability, micropenis, cryptorchidism, central hypothyroidism, and microcephaly. He had neonatal hypoglycemia at birth and later experienced refractory epileptic seizures and developed obesity and insulin-dependent diabetes. A diagnosis of MEHMO syndrome was established on the basis of the patient's clinical manifestations and de novo novel missense variant in the EIF2S3 gene (NM_001415.3:c.805â¯Tâ¯>â¯G) that was detected through whole-exome analysis. Although the patient's refractory seizures and diabetes had been well controlled with a combination of ketogenic diet (KD) therapy and insulin therapy, acute fatal necrotizing pancreatitis occurred at the age of 68â¯months. Moreover, despite intensive care, his condition rapidly deteriorated to multiple organ failure and acute respiratory distress syndrome, resulting in death. CONCLUSION: The pathophysiology of glucose intolerance in MEHMO syndrome remains to be elucidated; however, recent studies have suggested that EIF2S3 gene variants could lead to glucose dysregulation and ß-cell damage in the pancreas. We suspect that in the present case, KD therapy led to an abnormal load on the beta cells that were damaged owing to eIF2γ dysfunction. Therefore, the adverse effects of KD in patients with MEHMO syndrome should be considered.
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Dieta Cetogénica/efectos adversos , Epilepsia Refractaria/dietoterapia , Epilepsia Refractaria/etiología , Epilepsia/complicaciones , Genitales/anomalías , Hipogonadismo/complicaciones , Discapacidad Intelectual Ligada al Cromosoma X/complicaciones , Microcefalia/complicaciones , Obesidad/complicaciones , Pancreatitis Aguda Necrotizante/etiología , Preescolar , Epilepsia/diagnóstico , Resultado Fatal , Humanos , Hipogonadismo/diagnóstico , Masculino , Discapacidad Intelectual Ligada al Cromosoma X/diagnóstico , Microcefalia/diagnóstico , Obesidad/diagnóstico , Pancreatitis Aguda Necrotizante/diagnósticoRESUMEN
ObjectiveTo observe the effects of Wendantang on the expression of inflammatory cytokines, autophagy markers, and key molecules of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway in the adipocytes of the rat model of obesity (syndrome of phlegm-dampness) and to explore the material basis of inflammation in obesity (syndrome of phlegm-dampness) and the underlying mechanism of Wendantang intervention. MethodA total of 126 SD rats were randomized into 2 groups: 16 rats in the blank group and 110 rats in the modeling group. The blank group was fed with a basic diet while the modeling group with a high-fat diet to establish the animal model of obesity (syndrome of phlegm-dampness) for 8 weeks. After successful modeling, 48 obese rats were selected according to their body mass and randomized into a model control group, an orlistat (ORLI, 32.40 mg·kg-1) group, a rapamycin (RAPA, 2 mg·kg-1) group, and low-, medium-, and high-dose (4.45, 8.90, 17.80 g·kg-1, respectively) Wendantang groups, with 8 rats in each group. In addition, 8 rats were randomly selected from the blank group to be set as the normal control group. The corresponding agents in each group were administrated by gavage and the model and control groups were administrated with equal amounts of distilled water once daily for 6 weeks. The body mass, Lee's index, body fat ratio, and obesity rate were measured or calculated. The expression of UNC51-like kinase-1 (ULK1), Beclin1, human autophagy-related protein 5 (Atg5), p62, and microtubule-associated protein 1 light chain 3 (LC3) Ⅰ/Ⅱ (markers of autophagy in adipocytes) was detected by the immunohistochemical two-step method. Enzyme-linked immunosorbent assay (ELISA) was employed to determine the expression of tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-1β, monocyte chemotactic protein-1 (MCP-1), IL-4, IL-10, IL-13, and transforming growth factor (TGF)-β in adipocytes. Western blot was employed to measure the protein levels of classⅠ-PI3K, phosphatidylinositol triphosphate (PIP3), Akt, mTORC1, ULK1, TSC1, and TSC2 in adipocytes. ResultCompared with the blank group, the modeling group showed increased body mass and Lee's index (P<0.01), the obesity rate >20%, and phlegm-dampness syndrome manifestations such as physical obesity, decreased mobility, decreased appetite, lusterless and tight fur, loose stools, decreased responsiveness to the outside world, and decreased water intake. Compared with the normal control group, the model control group showed increased body mass, Lee's index, body fat ratio, adipocyte autophagy marker expression, pro- and anti-inflammatory cytokine levels (P<0.05, P<0.01), down-regulated protein levels of classⅠ-PI3K, PIP3, Akt, mTORC1, TSC1, and TSC2 (P<0.01), and up-regulated protein level of ULK1 (P<0.01). The intervention groups showed lower body mass, body fat ratio, adipocyte autophagy marker protein expression, and protein levels of TNF-α, IL-6, IL-1β, MCP-1, IL-4, and IL-13 than the model control group (P<0.05, P<0.01). Moreover, the RAPA and Wendantang (medium and high dose) groups showed lowered levels of IL-10 and TGF-β (P<0.01), and the ORLI group showed down-regulated expression of TGF-β (P<0.01). The expression of key molecules of the signaling pathway was up-regulated (P<0.05, P<0.01) while that of ULK1 was down-regulated (P<0.01) in all the intervention groups. Compared with the RAPA group, the Wendantang groups showed up-regulated expression of all autophagy marker proteins in adipocytes (P<0.01). In addition, the low-dose Wendantang group showed elevated levels of inflammatory cytokines (except TNF-α) (P<0.05, P<0.01) and down-regulated expression of all key molecules of the signaling pathway (P<0.05, P<0.01). The levels of inflammatory cytokines (except IL-16, MCP-1, and IL-10) were elevated in the medium-dose Wendantang group (P<0.05, P<0.01). The expression of key molecules except PI3K of the signaling pathway was down-regulated in the medium- and high-dose Wendantang groups (P<0.05, P<0.01). Compared with the ORLI group, low- and medium-dose Wendantang groups showed up-regulated expression of autophagy markers in adipocytes (P<0.01), and the low-dose group showed elevated levels of inflammatory cytokines (IL-6, IL-4, and TGF-β) (P<0.01) and down-regulated expression of all key molecules of the signaling pathway (P<0.01). The medium-dose Wendantang group showed up-regulated expression of IL-4 (P<0.01) and down-regulated expression of key molecules except PI3K of the signaling pathway (P<0.05, P<0.01). The high-dose Wendantang group showed increased body mass, up-regulated expression levels of autophagy markers (ULK1, LC3 Ⅰ/Ⅱ) (P<0.05, P<0.01), down-regulated expression of PIP3, mTORC1, and TSC1 (P<0.05, P<0.01), and lowered levels of Beclin1, Atg5, TNF-α, and IL-13 (P<0.05, P<0.01). ConclusionThe inflammation in obesity (syndrome of phlegm-dampness) is closely associated with the PI3K/Akt/mTOR pathway-mediated adipocyte autophagy. Wendantang can treat the chronic inflammation in obese rats with the syndrome of phlegm-dampness by regulating this signaling pathway and thus improve adipocyte autophagy.
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The association of anthropometric (waist circumference) and hemodynamic (blood pressure) changes with abnormalities in glucose and lipid metabolism has been motivation for a lot of discussions in the last 30 years. Nowadays, blood pressure, body mass index/abdominal circumference, glycemia, triglyceridemia, and HDL-cholesterol concentrations are considered in the definition of Metabolic syndrome, referred as Visceral adiposity syndrome (VAS) in the present review. However, more than 250 years ago an association between visceral and mediastinal obesity with hypertension, gout, and obstructive apnea had already been recognized. Expansion of visceral adipose tissue secondary to chronic over-consumption of calories stimulates the recruitment of macrophages, which assume an inflammatory phenotype and produce cytokines that directly interfere with insulin signaling, resulting in insulin resistance. In turn, insulin resistance (IR) manifests itself in various tissues, contributing to the overall phenotype of VAS. For example, in white adipose tissue, IR results in lipolysis, increased free fatty acids release and worsening of inflammation, since fatty acids can bind to Toll-like receptors. In the liver, IR results in increased hepatic glucose production, contributing to hyperglycemia; in the vascular endothelium and kidney, IR results in vasoconstriction, sodium retention and, consequently, arterial hypertension. Other players have been recognized in the development of VAS, such as genetic predisposition, epigenetic factors associated with exposure to an unfavourable intrauterine environment and the gut microbiota. More recently, experimental and clinical studies have shown the autonomic nervous system participates in modulating visceral adipose tissue. The sympathetic nervous system is related to adipose tissue function and differentiation through beta1, beta2, beta3, alpha1, and alpha2 adrenergic receptors. The relation is bidirectional: sympathetic denervation of adipose tissue blocks lipolysis to a variety of lipolytic stimuli and adipose tissue send inputs to the brain. An imbalance of sympathetic/parasympathetic and alpha2 adrenergic/beta3 receptor is related to visceral adipose tissue storage and insulin sensitivity. Thus, in addition to the well-known factors classically associated with VAS, abnormal autonomic activity also emerges as an important factor regulating white adipose tissue, which highlights complex role of adipose tissue in the VAS.
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The ageing process is accompanied by osteoporosis,sarcopenia and obesity,which are named as osteosarcopenic obesity(OSO)syndrome.It is a recently identified syndrome characterized by simultaneous presence of osteopenia/osteoporosis,sarcopenia and increased adiposity(obesity),with a potential interconnection within these diseases via common pathophysiology.OSO is harmful for the elderly's physical-mental health and living quality,especially for bone fracture.Therefore,we reviewed a research progress on the relationship between OSO and fractures in the elderly.
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Síndrome de Prader-Willi/complicaciones , Síndrome de Prader-Willi/terapia , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/etiología , Cirugía Bariátrica , Composición Corporal , Niño , Trastornos de la Conducta Infantil/etiología , Diabetes Mellitus Tipo 2/etiología , Dieta Reductora , Enanismo/etiología , Metabolismo Energético , Ghrelina/sangre , Hormonas Esteroides Gonadales/deficiencia , Terapia de Reemplazo de Hormonas , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Hiperfagia/etiología , Hipogonadismo/etiología , Hipotiroidismo/etiología , Trastornos Mentales/etiología , Obesidad/complicaciones , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Trastornos del Sueño-Vigilia/etiologíaRESUMEN
The safe clinical practice of growth hormone(GH) replacement requires judgement of the overall GH status, however, there is no biological marker for this in adults. In addition, diverse actions of GH in healthy individuals render the assessment of optimal GH replacement difficult. As in other fields of clinical practice, strategies and protocols vary between centers, however, most physicians experienced in pituitary diseases agree that GH replacement should begin at low doses, and increased to the final maintenance dose. The adequacy replacement is best determined by combination of clinical response and serum IGF-I, level avoiding supraphysiological levels of this GH-dependent peptide. Actually, GH can reduce body fat and restore muscles, bones, and quality of life. Appropriate using of GH will elicit antiaging effects.