RESUMEN
AIM: Peroxisome proliferator-activated receptor γ (PPAR γ) is a critical factor for some pathways that involve in adipogenesis and osteogenesis. The aim of study was to compare PPARγ gene expression, different cytokines' levels and bone markers in osteopenic and non-osteopenic obese subjects. METHODS: A total of 265 obese participants recruited in the current case-control cross sectional study. BMD at region of lumbar spine and hip were measured in all participants. We categorized all participants into two osteopenic and non-osteopenic groups. RESULTS: Of the 265 obese participants, 77 (29.05 %) were osteopenic and 188 (70.95%) were non-osteopenic. We found significantly higher concentration of crosslaps and IL6 and lower free fat mass in osteopenic group. The relative gene expression of PPAR γ in osteopenic group was significantly higher than non-osteopenic group. Based on relative gene expression tertiles participants were rearranged all participants into two new groups; low expressed PPAR γ with low PPAR γ gene expression≤75% and high expressed PPAR γ with PPAR γ gene expression>75%. The levels of fat percents, triglyceride, LDL, HDL and total cholesterol in high expressed PPAR γ group were significantly higher than low expressed PPAR γ group. Also, significantly higher concentration of IL10, IL6 and TNFα and lower concentration of hs-CRP were detected in high expressed group compare to low expressed PPAR γ group. The BMD, T-score and Z-score in high expressed PPAR γ group were lower than low expressed PPAR γ group. CONCLUSION: Our findings suggest that the over expression of PPARγ in obese individual's PBMCs may have a critical role in relationship between obesity and bone loss. Further studies recommended clarifying the mechanism of PPARγ in bone turnover in obese subjects.
Asunto(s)
Densidad Ósea , Enfermedades Óseas Metabólicas/metabolismo , Obesidad/metabolismo , PPAR gamma/metabolismo , Adulto , Estudios de Casos y Controles , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Obesidad/sangre , Triglicéridos/sangre , Regulación hacia ArribaRESUMEN
AIM: The underlying molecular mechanisms of the role obesity plays in increasing the risk of cancer are not well illuminated. Several mechanisms are proposed for vitamin D as an anti-cancer agent in various malignancies which may be attributed to both its both its anti-inflammatory characteristics as well as its mediatory role in cellular energy homeostasis. This study evaluates the expression of PBMCs' genes which are involved in cellular energy homeostasis such as VDR, PPARγ, PGC1a and UCP2. Moreover, considering the possible role of vitamin D in the inflammation mechanisms, we also aimed at measurement of some inflammatory mediators such as TNF-α, IL-1ß, IL4, IL-6, IL10, IL13 and IL17 in inflammatory state in samples obtained from obese persons with and without positive family history of cancer. Moreover, to expand the study to a clinical context, we assessed the correlation of the resting metabolic rate with the evaluated gene. METHODS: A total of 274 obese women were included in the current cross-sectional study. All of participants were class I obese. By constructing a pedigree that includes 3 generations, twenty-one subjects were at increased risk because of a positive family history of colorectal cancer. Accordingly, current study's analysis was based on positive and negative family history of colorectal cancer. RESULTS: The concentration of Insulin and PTH were significantly high in group with positive history of cancer. 25 (OH) vitamin D, REE/kg and REE/FFM statuses in two groups; the level of mentioned terms were lower in group with positive history of cancer compared to group with negative history of cancer. We found significantly lower REE/kg in deficiency of vitamin D and higher REE/kg in sufficiency status. Our results demonstrated significant higher concentrations of IL1ß, IL17, TNFα and IL6 in group with positive history of cancer compared to group with negative history of cancer. The concentrations of IL13, IL10 and IL4 were significantly lower in group with positive history of cancer compared to group with negative history of cancer. The relative expression of VDR, PGC1αand PPARγ gene was significantly lower in group with positive history of cancer. The relative expression of UCP2 was almost significantly lesser in group with positive history of cancer also. CONCLUSION: The observed mutual alteration in the levels of inflammatory markers and relative expression of important gene in energy homeostasis may be caused by vitamin D deficiency among the obese subjects with positive history of colorectal cancer.
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Homeostasis , Mediadores de Inflamación/metabolismo , Inflamación/metabolismo , Obesidad/metabolismo , Vitamina D/fisiología , Adulto , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/genética , Estudios Transversales , Femenino , Expresión Génica , Proteínas de Choque Térmico/sangre , Humanos , Insulina/sangre , Interleucinas/sangre , Obesidad/genética , PPAR gamma/sangre , Hormona Paratiroidea/sangre , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Receptores de Calcitriol/sangre , Factores de Transcripción/sangre , Factor de Necrosis Tumoral alfa/sangreRESUMEN
AIM: The aim of the study was to measure circulating PGRN levels and to investigate its potential correlation with resting metabolic rate and obesity related complications. Moreover, to investigate on the PGRN and some important gene expressions in energy expenditure in vitro in samples of PBMCs derived from all participants of our study in a cellular model. METHODS: Of the 163 participants who were recruited for the current cross-sectional study, 37 (22.69%) were normal weight (18.5≤BMI<25), 53 (32.51%) were overweight (25≤BMI<30), 48 (29.44%) were categorized as class I obese (BMI 30 -34.9) and 25 (15.33%) were classified as class II and III obese (BMI≥35). All participants were assessed for the measurement of RMR by means of indirect calorimetry following an overnight fasting. Body composition was analyzed with the Bioelectrical Impedance technique by the BODY COMPOSITION ANALYZER BC-418M -Tanita. The PBMCs were separated from whole blood by Ficoll-hypaque technique. Total cellular RNA was extracted and the cDNA was synthesized. This process was followed by real-time PCR using specific primer pairs for PGRN, AKT, MAPK and mRNA, and beta actin mRNA was used as the internal control. Circulating PGRN was measured with the use of ELISA method. RESULTS: The circulating levels and gene expressions of PGRN rose in parallel with the increase of body weight. However, there was significant difference in the strength of association between circulating PGRN as well as PGRN gene expression and obesity-related variables. Moreover, PGRN gene expression had significant correlation with BMI, visceral fat, MAPK and AKT gene expression. The increased mass of visceral fat in correlation with the increased PGRN levels was more pronounced in high or normal resting metabolic rate group compared with the group with low resting metabolic rate. After adjusting for BMI and gender, we found that circulating PGRN can predict the RMR/kg independent of other variables such as TG, HDL, and hs-CRP (P=0.03). CONCLUSION: PGRN associated with obesity and glucose homeostasis and may predict the resting metabolic rate levels independent of confounder factors. Experimental study may clarify the PGRN role in obesity etiology through metabolism regulation.
Asunto(s)
Metabolismo Basal , Inflamación/metabolismo , Péptidos y Proteínas de Señalización Intercelular/sangre , Obesidad/metabolismo , Adulto , Algoritmos , Biomarcadores/sangre , Composición Corporal , Índice de Masa Corporal , Estudios Transversales , Impedancia Eléctrica , Femenino , Regulación de la Expresión Génica , Humanos , Inflamación/sangre , Péptidos y Proteínas de Señalización Intercelular/genética , Masculino , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/sangre , Obesidad/sangre , Sobrepeso/metabolismo , Progranulinas , Proteínas Proto-Oncogénicas c-akt/sangre , ARN Mensajero/sangre , MuestreoRESUMEN
AIM: The aim of the study was to investigate the concentration of PGRN and other inflammatory cytokines TNF-α, IL-1ß, IL-4, IL-6, IL-10, IL-13 and IL-17 in osteopenic and non-osteopenic obese subjects. Bone mineral density in subjects with different PGRN levels were compared to the appraisal of our hypothesis. METHODS: A total of 171 obese participants (BMI ≥30) were included in the study. Analysis of body composition was performed with use of Body Composition Analyzer. All blood samples were collected between 8:00 and 10:00 a.m. following an overnight fasting. The circulating levels of TNF-α, PGRN, IL-1ß, IL-4, IL-6, IL-10, IL-13, IL-17, PTH, 25-Hydroxy Vitamin D and crosslaps were measured with the EIA method. BMD was measured by use of dual energy X-ray absorptiometery (DXA) at lumbar spine (vertebrae L2-L4) and hip level. Participants were categorized into osteopenic and healthy group according to the World Health Organization (WHO) criteria. Of 171 participants, 51 (29.82 %) were osteopenic and 120 (70.17%) were healthy. RESULTS: We found significantly higher concentrations of crosslaps, IL-17, IL-6, TNFα and IL-4 and lower concentrations of IL-13, IL-10, PGRN and free fat mass in osteopenic group. With raising the PGRN level, the concentrations of IL-13, IL-10 and 25-(OH) vitamin D were increased and the concentration of TNFα and IL-17 were decreased. Our results demonstrated that the density of bone at both sites of lumbar spine (L2-L4) and hip region was highest in 4th quartile and lowest in first quartile of categorized PGRN concentration. The bone status was gradually improved with raising the PGRN level in parallel at lumbar spine (L2-L4) and hip regions. CONCLUSION: Based on the pathway of effect of TNFα on bone metabolism, it appears that PGRN acts on the bone with mechanisms involving TNFR signaling, disturbance and TNFα performance, similar to the results that have been found in animal model study.