OBJECTIVE: The age of adiposity rebound (AR) is defined as the time at which BMI starts to rise after infancy and is thought to be a marker of later obesity. To determine whether this age is related to future occurrence of metabolic syndrome, we investigated the relationship of the timing of AR with metabolic consequences at 12 years of age. METHODS: A total of 271 children (147 boys and 124 girls) born in 1995 and 1996 were enrolled in the study. Serial measurements of BMI were conducted at the ages of 4 and 8 months and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 years, based on which age of AR was calculated. Plasma lipids and blood pressure were measured at 12 years of age. RESULTS: An earlier AR (<4 years of age) was associated with a higher BMI (≥20) and a lipoprotein phenotype representative of insulin resistance. This phenotype consists of elevated triglycerides, apolipoprotein B, and atherogenic index and decreased high-density lipoprotein cholesterol in boys and elevated apolipoprotein B in girls at 12 years of age. The earlier AR was also related to elevated blood pressure in boys. CONCLUSIONS: This longitudinal population-based study indicates that children who exhibit AR at a younger age are predisposed to future development of metabolic syndrome. Therefore, monitoring of AR may be an effective method for the early identification of children at risk for metabolic syndrome.

The IGF axis is critical for the regulation of apoptosis in many human cancer cell lines. Recently, potent anti-tumorigenic effects of pomegranate juice and extracts have been reported. Consequently, pomegranate has potential not only as a treatment but also as a preventative measure against certain types of cancer, including prostate. In this study, we investigated the relationship between pomegranate-induced apoptosis in human prostate cancer cells and the IGF/IGFBP system. Treatment of LAPC4 prostate cancer cells with 10 μg/ml POMx, a highly potent pomegranate extract prepared from skin and arils minus seeds and standardized to ellagitannin content (37% punicalagins by HPLC), resulted in inhibition of cell proliferation and induction of apoptosis. Interestingly, cotreatment with POMx and IGFBP-3 revealed synergistic stimulation of apoptosis and additive inhibition of cell growth. Western blot analysis revealed that treatment with POMx or POMx/ IGFBP-3 combination resulted in increased JNK phosphorylation, and decreased Akt and mTOR activation, consistent with a growth inhibitory, pro-apoptotic function. We also investigated the relationship between IGF-1 and pomegranate-induced apoptosis in 22RV1 prostate cancer cells. Cotreatment with 100 ng/ml IGF-1 completely blocked apoptosis induction by POMx. In contrast, IGF-I failed to inhibit POMx-induced apoptosis in R-cells, suggesting the importance of IGF-IR. POMxtreatment decreased Igf1 mRNA expression in a dose-dependent manner indicating that its actions also involve tumor-specific suppression of IGF-1. These studies revealed novel interactions between the IGF system and pomegranate-induced apoptosis.

. Dynamic changes in body weight have long been recognized as important indicators of risk for human health. Many population-based observational studies have shown that rapid weight gain during infancy, including a catch-up growth phenomenon or adiposity rebound in early childhood, predisposes a person to the development of obesity, type 2 diabetes, and cardiovascular diseases later in life. However, a consensus has not been established regarding which period of weight gain contributes to future risks. This review evaluates recent evidence on the relationship between early rapid growth and future obesity and cardiometabolic risk, with a focus on the differential significance of rapid weight gain in infancy and early childhood. Although there is a need for attention to childhood growth during early infancy before 1 yr of age as it may be related to future obesity, emerging evidence strongly suggests that toddlers showing an increase in body mass index (BMI) before 3 yr of age, a period normally characterized by decreased BMI, are prone to developing later cardiometabolic risk.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is one of the most common inherited metabolic diseases. We studied 52 Japanese 21-hydroxylase deficiency patients corresponding to 49 families (98 chromosomes) to detect the mutations in 21-hydroxylase genes using Southern blotting, PCR-restriction fragment length polymorphism, and a direct sequencing method. Among the 52 patients (49 families), 35 patients (33 families) were diagnosed as the salt-wasting type, 12 (12 families) as the simple virilizing type, and 5 (4 families) as the nonclassical type. Our findings were as follows. 1) The complete genotype that had homozygous or compound heterozygous mutations was determined in 43 of 49 families (87.8%). Among the remaining patients, no mutation was found in the structural gene of either allele in 3 cases, and a mutation was detected in only 1 allele in 3 cases. This means that at least 9 of 98 alleles have some unusual mutations or recombinations that we cannot detect by our method or gene defects outside of the structural gene. 2) Although the common mutation of Caucasian nonclassical patients is V281L, none of our 4 nonclassical families showed this mutation, and 3 of them had the P30L mutation at least on 1 allele. 3) We identified a putative new mutation, homozygous deletion of adenine at codon 246, in a salt-wasting patient. Although we have not analyzed the functional consequence of this mutation, it causes substitution noncoding for Met(256) in exon 7 and premature termination of the mRNA before the heme-binding region of the P450 polypeptide, which would result in a completely nonfunctional enzyme.