Sweeten, Shawn

The aim of the study was to evaluate the effect of severe short‐term nutritional deprivation (ND) on the fractional synthesis rates (FSR) specific proteins and protein pools in the diaphragm muscle (DiaM). Male rats were divided into two groups: 20% of usual food intake for 4 days (ND) with water provided at libitum and free‐eating control (Ctl). [U‐13‐C] leucine was continuously infused through the jugular vein for 3–3.5 h after a priming dose of the isotope. Blood samples were collected from the carotid artery at baseline and every 30 min at precursor pool plateau. DiaM was excised at the end of the isotope infusion. Mixed muscle protein (MMP), myosin heavy chain (MHC), sarcoplasmic (Sarco) and mitochondrial (Mito) proteins were extracted from DiaM and the incorporation of the label into each protein(s) was determined using mass spectrometry. The FSR of MMP, MHC, Sarco and Mito in the rat DiaM were calculated using the precursor‐product relationship. ND resulted in the reduction of the FSRs of MMP (71%), MHC (69%), Sarco (44%) and Mito (55%) in DiaM. In summary, short‐term ND is associated with a global decrease in the synthetic rate of DiaM proteins, suggesting a compromise in the ability of the DiaM to synthesize functionally important proteins in the ND state. The underlying mechanisms for this depressed state of protein synthesis in DiaM related to ND remain to be elucidated.

Abstract Background: Metabolic syndrome (MS)-related comorbidities in obesity, such as hypertension, dyslipidemia, and glucose intolerance, are increasingly recognized in children, predisposing them to early cardiovascular disease. Objective: The objective of the study was to investigate whether markers of inflammation and prothrombosis are abnormal in obese children without established MS comorbidities across puberty, as compared with lean, age-matched controls. Subjects and Methods: Obese children (body mass index >95%) with normal fasting glucose, blood pressure, cholesterol and triglycerides were recruited; lean controls (body mass index 10–75%) had no first-degree relatives with MS. High-sensitivity C-reactive protein (hsCRP), IL-6, plasminogen activator inhibitor 1, and fibrinogen concentrations were measured. Body composition was assessed by waist circumference and dual-energy x-ray absorptiometry. Results: Of 623 children screened, 203 enrolled (106 males, 97 females), aged 7–18 yr, 115 obese, 88 lean (balanced for age and gender), 99 prepubertal, and 104 pubertal. Many screen failures were due to silent comorbidities. Obese subjects with insulin resistance but without MS comorbidities had about 10 times higher hsCRP concentrations than controls and higher fibrinogen, IL-6, and plasminogen activator inhibitor-1 (P < 0.01 all). Differences were significant, even in the prepubertal cohort. hsCRP and fibrinogen correlated with waist circumference (r = 0.73 and 0.40, respectively) and percent fat mass (r = 0.76 and 0.47) (P < 0.0001). Conclusion: Childhood obesity per se is associated with a proinflammatory and prothrombotic state before other comorbidities of the MS are present and even before the onset of puberty. Whether biomarkers like hsCRP and fibrinogen are useful in assessing cardiovascular risk and whether these abnormalities are reversible with earlier therapeutic interventions in very young obese children requires further study.