RESUMO
BACKGROUND: Obesity is defined as a multifactorial disease, marked by excessive accumulation of body fat, responsible for compromising the individual's health over the years. The energy balance is essential for the proper functioning of the body, as the individual needs to earn and spend energy in a compensatory way. Mitochondrial Uncoupling Proteins (UCP) help in energy expenditure through heat release and genetic polymorphisms could be responsible for reducing energy consumption to release heat and consequently generate an excessive accumulation of fat in the body. Thus, this study aimed to investigate the potential association between six UCP3 polymorphisms, that have not yet been represented in ClinVar®, and pediatric obesity susceptibility. METHODS: A case-control study was conducted with 225 children from Central Brazil. The groups were subdivided into obese (123) and eutrophic (102) individuals. The polymorphisms rs15763, rs1685354, rs1800849, rs11235972, rs647126, and rs3781907 were determined by real-time Polymerase Chain Reaction (qPCR). RESULTS: Biochemical and anthropometric evaluation of obese group showed higher levels of triglycerides, insulin resistance, and LDL-C and low level of HDL-C. Insulin resistance, age, sex, HDL-C, fasting glucose, triglyceride levels, and parents' BMI explained up to 50% of body mass deposition in the studied population. Additionally, obese mothers contribute 2 × more to the Z-BMI of their children than the fathers. The SNP rs647126 contributed to 20% to the risk of obesity in children and the SNP rs3781907 contribute to 10%. Mutant alleles of UCP3 increase the risk for triglycerides, total cholesterol, and HDL-C levels. The polymorphism rs3781907 is the only one that could not be a biomarker for obesity as the risk allele seem to be protective gains the increase in Z-BMI in our pediatric population. Haplotype analysis demonstrated two SNP blocks (rs15763, rs647126, and rs1685534) and (rs11235972 and rs1800849) that showed linkage disequilibrium, with LOD 76.3% and D' = 0.96 and LOD 57.4% and D' = 0.97, respectively. CONCLUSIONS: The causality between UCP3 polymorphism and obesity were not detected. On the other hand, the studied polymorphism contributes to Z-BMI, HOMA-IR, triglycerides, total cholesterol, and HDL-C levels. Haplotypes are concordant with the obese phenotype and contribute minimally to the risk of obesity.
Assuntos
Resistência à Insulina , Obesidade Infantil , Proteína Desacopladora 3 , Criança , Humanos , Índice de Massa Corporal , Estudos de Casos e Controles , Colesterol , Frequência do Gene , Genótipo , Obesidade Infantil/genética , Polimorfismo de Nucleotídeo Único , Triglicerídeos , Proteína Desacopladora 3/genéticaRESUMO
The medicinal uses of Calotropis procera are diverse, yet some of them are based on effects that still lack scientific support. Control of diabetes is one of them. Recently, latex proteins from C. procera latex (LP) have been shown to promote in vivo glycemic control by the inhibition of hepatic glucose production via AMP-activated protein kinase (AMPK). Glycemic control has been attributed to an isolated fraction of LP (CpPII), which is composed of cysteine peptidases (95%) and osmotin (5%) isoforms. Those proteins are extensively characterized in terms of chemistry, biochemistry and structural aspects. Furthermore, we evaluated some aspects of the mitochondrial function and cellular mechanisms involved in CpPII activity. The effect of CpPII on glycemic control was evaluated in fasting mice by glycemic curve and glucose and pyruvate tolerance tests. HepG2 cells was treated with CpPII, and cell viability, oxygen consumption, PPAR activity, production of lactate and reactive oxygen species, mitochondrial density and protein and gene expression were analyzed. CpPII reduced fasting glycemia, improved glucose tolerance and inhibited hepatic glucose production in control animals. Additionally, CpPII increased the consumption of ATP-linked oxygen and mitochondrial uncoupling, reduced lactate concentration, increased protein expression of mitochondrial complexes I, III and V, and activity of peroxisome-proliferator-responsive elements (PPRE), reduced the presence of reactive oxygen species (ROS) and increased mitochondrial density in HepG2 cells by activation of AMPK/PPAR. Our findings strongly support the medicinal use of the plant and suggest that CpPII is a potential therapy for prevention and/or treatment of type-2 diabetes. A common epitope sequence shared among the proteases and osmotin is possibly the responsible for the beneficial effects of CpPII.
RESUMO
Mitochondrial uncoupling proteins (UCPs) are mitochondrial inner membrane proteins that dissipate the proton electrochemical gradient generated by the respiratory chain complexes. In plants, these proteins are crucial for maintaining mitochondrial reactive oxygen species (ROS) homeostasis. In this study, single T-DNA insertion mutants for two (AtUCP1 and AtUCP2) out of the three UCP genes present in Arabidopsis thaliana were employed to elucidate their potential roles in planta. Our data revealed a significant increase in the Adenosine triphosphate (ATP)/Adenosine diphosphate (ADP) ratios of both mutants, indicating clear alterations in energy metabolism, and a reduced respiratory rate in atucp2. Phenotypic characterization revealed that atucp1 and atucp2 plants displayed reduced primary root growth under normal and stressed conditions. Moreover, a reduced fertility phenotype was observed in both mutants, which exhibited an increased number of sterile siliques and a lower seed yield compared with wild-type plants. Reciprocal crosses demonstrated that both male fertility and female fertility were compromised in atucp1, while such effect was exclusively observed in the male counterpart in atucp2. Most strikingly, a pronounced accumulation of hydrogen peroxide in the reproductive organs was observed in all mutant lines, indicating a disturbance in ROS homeostasis of mutant flowers. Accordingly, the atucp1 and atucp2 mutants exhibited higher levels of ROS in pollen grains. Further, alternative oxidase 1a was highly induced in mutant flowers, while the expression profiles of transcription factors implicated in gene regulation during female and male reproductive organ/tissue development were perturbed. Overall, these data support the important role for AtUCP1 and AtUCP2 in flower oxidative homeostasis and overall plant fertility.