Faculty Bibliography

Expansion of bone marrow (BM) adipocytes has been linked to nutritional pressures, suggesting that BM is a dynamic compartment that responds to fluctuations in systemic nutritional availability to regulate osteogenesis and hematopoiesis. Here, we investigated BM metabolism in response to acute overnutrition (high calorie diet; HCD) and calorie deprivation (fasting). Participants underwent a 10-day HCD followed by a two-week interval of an ad libitum diet and then underwent 10 days of fasting. BM adipocytes and sera were collected before and after each dietary intervention for each participant. Using comprehensive and integrated analyses, we characterized nutritional influences on BM adiposity. BM adipocytes after HCD showed an upregulation of FOXP3, the transcription factor that controls the development of Tregs, which are critical in reducing inflammatory immune responses. After fasting, BM adipocytes had an upregulation of inflammatory genes (CP, CFH, VCAN, and IGFBP3). Proteomic analysis after HCD showed that BM serum had an upregulation of proteins related to an inflammatory/complement pathway. After fasting, in the BM serum, there was a significant downregulation of inflammatory/complement pathway proteins. Despite both interventions causing BM adipose tissue expansion, the mechanism for adipogenesis appears to be dependent on nutrient availability. After HCD, lipid-mediated signaling and lipid storage, and lipid droplet biogenesis were significantly downregulated. In contrast, after fasting, lipid-mediated signaling and lipid storage, and lipid droplet biogenesis were significantly upregulated. Overall, our results demonstrate key differences in inflammatory response and lipid metabolism between HCD and fasting, despite a nearly identical BM adipose phenotype. Further analyses are needed to understand the effects nutritional pressures have on BM adipogenesis and immune responses.

Osteoporosis is underdiagnosed, especially in ethnic and racial minorities who are thought to be protected against bone loss, but often have worse outcomes after an osteoporotic fracture. We aimed to determine the prevalence of osteoporosis by opportunistic CT in patients who underwent lung cancer screening (LCS) using non-contrast CT in the Northeastern United States. Demographics including race and ethnicity were retrieved. We assessed trabecular bone and body composition using a fully-automated artificial intelligence algorithm. ROIs were placed at T12 vertebral body for attenuation measurements in Hounsfield Units (HU). Two validated thresholds were used to diagnose osteoporosis: high-sensitivity threshold (115-165 HU) and high specificity threshold (<115 HU). We performed descriptive statistics and ANOVA to compare differences across sex, race, ethnicity, and income class according to neighborhoods' mean household incomes. Forward stepwise regression modeling was used to determine body composition predictors of trabecular attenuation. We included 3708 patients (mean age 64 ± 7 years, 54 % males) who underwent LCS, had available demographic information and an evaluable CT for trabecular attenuation analysis. Using the high sensitivity threshold, osteoporosis was more prevalent in females (74 % vs. 65 % in males, p < 0.0001) and Whites (72 % vs 49 % non-Whites, p < 0.0001). However, osteoporosis was present across all races (38 % Black, 55 % Asian, 56 % Hispanic) and affected all income classes (69 %, 69 %, and 91 % in low, medium, and high-income class, respectively). High visceral/subcutaneous fat-ratio, aortic calcification, and hepatic steatosis were associated with low trabecular attenuation (p < 0.01), whereas muscle mass was positively associated with trabecular attenuation (p < 0.01). In conclusion, osteoporosis is prevalent across all races, income classes and both sexes in patients undergoing LCS. Opportunistic CT using a fully-automated algorithm and uniform imaging protocol is able to detect osteoporosis and body composition without additional testing or radiation. Early identification of patients traditionally thought to be at low risk for bone loss will allow for initiating appropriate treatment to prevent future fragility fractures. CLINICALTRIALS.GOV IDENTIFIER: N/A.

BACKGROUND:Accumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity. METHODS:], and liver fat fraction [proportion; range, 0 to 1; higher values indicate a higher proportion of fat]), and resting energy expenditure (kcal/day; adjusted for lean mass) from baseline to week 8 and caloric intake (kcal) at an experimental test meal from baseline to week 6. RESULTS:[-11.0 to 17.2]; liver fat: -0.01 [-0.03 to 0.01]; resting energy expenditure: -64.0 kcal/day [-129.3 to 1.4]). Oxytocin compared with placebo was associated with reduced caloric intake at the test meal (-31.4 vs. 120.6 kcal; difference [95% confidence interval], -152.0 kcal [-302.3 to -1.7]). There were no serious adverse events. Incidence and severity of adverse events did not differ between groups. CONCLUSIONS:In this randomized, placebo-controlled trial in adults with obesity, intranasal oxytocin administered four times daily for 8 weeks did not reduce body weight. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT03043053.).

The purpose of this study was to assess the value of body composition measures obtained from opportunistic abdominal computed tomography (CT) in order to predict hospital length of stay (LOS), 30-day postoperative complications, and reoperations in patients undergoing surgery for spinal metastases. 196 patients underwent CT of the abdomen within three months of surgery for spinal metastases. Automated body composition segmentation and quantifications of the cross-sectional areas (CSA) of abdominal visceral and subcutaneous adipose tissue and abdominal skeletal muscle was performed. From this, 31% (61) of patients had postoperative complications within 30 days, and 16% (31) of patients underwent reoperation. Lower muscle CSA was associated with increased postoperative complications within 30 days (OR [95% CI] = 0.99 [0.98-0.99], p = 0.03). Through multivariate analysis, it was found that lower muscle CSA was also associated with an increased postoperative complication rate after controlling for the albumin, ASIA score, previous systemic therapy, and thoracic metastases (OR [95% CI] = 0.99 [0.98-0.99], p = 0.047). LOS and reoperations were not associated with any body composition measures. Low muscle mass may serve as a biomarker for the prediction of complications in patients with spinal metastases. The routine assessment of muscle mass on opportunistic CTs may help to predict outcomes in these patients.