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.

To elucidate the effect of early growth patterns on the metabolic sensitivity to adiposity, we examined the relationship between the homeostatic model assessment of insulin resistance (HOMA-IR) and body mass index (BMI) levels at 12 years of age in 101 boys and 91 girls in a birth cohort. Children with an increase in BMI from the ages of 1.5 to 3 years exhibited a greater increase of HOMA-IR per BMI increase at 12 years of age compared to those with a decrease in BMI or stable BMI from 1.5 to 3 years. This suggests that children who show an increase in BMI from 1.5 to 3 years, a period normally characterized by a decreased or stable BMI, are more prone to developing insulin resistance at 12 years of age.

We examined the effects of cannabinoid receptor agonists on various respiratory reactions induced by the activation of capsaicin-sensitive afferent sensory nerves (C-fibers). (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-merpholino)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone (WIN 55212–2) dose-dependently inhibited electrical field stimulation– and capsaicin-induced guinea pig bronchial smooth muscle contraction, but not the neurokinin A–induced contraction. A cannabinoid CB2 receptor antagonist, {N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide} (SR 144528), reduced the inhibitory effect of WIN 55212–2, but not a cannabinoid CB1 antagonist, [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride] (SR 141716A). A cannabinoid CB2 agonist, JWH 133, also inhibited electrical field stimulation–induced guinea pig bronchial smooth muscle contraction and its inhibitory effect was blocked by SR 144528. The inhibitory effect of WIN 55212–2 on electrical field stimulation-induced bronchial contraction was reduced by the pretreatment of large conductance Ca2+-activated K+ channel (Maxi-K+ channel) blockers, iberiotoxin and charybdotoxin, but not other K+ channel blockers, dendrotoxin or glibenclamide. A Maxi-K+ channel opener, 1-(2′-hydroxy-5′-trifluoromethylphenyl)-5-trifluoromethyl-2(3H)benzimidazolone (NS1619), inhibited bronchial contraction induced by electrical field stimulation. WIN 55212–2 and JWH 133 blocked the capsaicin-induced release of substance P-like immunoreactivity from guinea pig airway tissues. These findings suggest that WIN 55212–2 inhibit the activation of C-fibers via cannabinoid CB2 receptors and Maxi-K+ channels in guinea pig airways.

Purpose: We investigated the relationship of 25-hydroxyvitamin D (25[OH]D) level with obesity and atherosclerosis in Japanese adolescents.Methods: We examined 492 children (247 boys and 245 girls) aged 12–13 years. The serum 25(OH)D level was compared among underweight, healthy weight, and overweight children. Spearman correlation coefficient analysis was performed to examine the relationships between the 25(OH)D level and body mass index (BMI), plasma lipids, and blood pressure and to compare the latter between the normal (≥20 ng/mL) and low (<20 ng/mL) 25(OH)D groups. Further, we performed a multiple regression analysis to assess the effect on the 25(OH)D level.Results: The serum 25(OH)D level was significantly lower in overweight (20.5±2.7 ng/mL) than in healthy-weight boys (22.4±3.3 ng/mL) (P=0.004). Spearman correlation coefficients comparing the relationship of the 25(OH)D level with BMI, high-density lipoprotein cholesterol (HDL-C), and atherogenic index indicated significance in boys (ρ=-0.238 [P<0.0001], ρ=0.197 [P=0.002], and ρ=-0.146 [P=0.022], respectively). In boys, the multiple regression analysis results showed that BMI had negative and HDL-C had positive effects on the 25(OH)D level. The first was higher and the latter was lower in boys with low 25(OH)D level than in those with normal levels, respectively (P<0.05). No significant correlations were detected in girls.Conclusion: Low serum 25(OH)D level was associated with obesity and increased atherogenic risk in adolescent boys only. This sex difference was probably mediated by body composition, sun exposure, estrogen, and adiponectin, which are characteristics of puberty.

To clarify the relationship between the expression of atherogenic small, dense low-density lipoprotein (SDLDL) and underlying lipid metabolic abnormalities, the prevalence of SDLDL in relation to the serum lipid phenotype was analyzed in 229 children. The LDL particle size was measured using gradient gel electrophoresis, and a particle size of less than 25.5 nm was considered to represent SDLDL. The overall prevalence of SDLDL in the sample population was 8.2% (19/229; 11/117 for boys and 8/112 for girls). Hyperlipidemia phenotype IIb (elevated concentrations of both triglyceride [TG] and total cholesterol [TC]) was strongly associated with SDLDL in 83% (5/6) of the subjects. An elevated TG concentration (phenotype IV) was associated with SDLDL in 55% (10/18) of the subjects. The association between hyperlipidemia phenotype IIa (elevated TC but a normal TG concentration) and SDLDL was quite low (2%; 1/56), but SDLDL was detected in 5% (8/155) of the subjects who presented with normolipidemia. Therefore, these findings suggest that the expression of SDLDL is largely related to lipid abnormalities characterized by phenotype IIb or IV, the underlying metabolic abnormality of which is suspected to be insulin resistance; however, an additional mechanism for the formation of SDLDL that functions independently of plasma lipid abnormalities also seems to exist.