Influence of Free Fatty Acid Concentrations and Weight Loss on Adipose Tissue Direct Free Fatty Acid Storage Rates.

CONTEXT: The factors that determine the recycling of free fatty acids (FFA) back into different adipose tissue depots via the direct storage pathway are not completely understood. OBJECTIVE: To assess the interactions between adipocyte factors and plasma FFA concentrations that determine regional FFA storage rates. DESIGN: We measured direct adipose tissue FFA storage rates before and after weight loss under high FFA (intravenous somatostatin and epinephrine) and low (intravenous insulin and glucose) FFA concentrations. SETTING: Mayo Clinic Clinical Research Unit. PATIENTS: Sixteen premenopausal women, body mass index 30 to 37 kg/m2. INTERVENTION: Comprehensive lifestyle weight loss program. MAIN OUTCOME MEASURE: Direct FFA storage rates in upper and lower body subcutaneous fat. RESULTS: Over the entire range of FFA and under isolated conditions of elevated FFA concentrations, the storage rates of FFA into upper and lower body subcutaneous fat per unit lipid were associated with concentrations, not adipocyte fatty acid storage factors. Under low FFA conditions, direct FFA storage rates were related to adipocyte CD36 content, not tissue level content of fatty acid storage factors. Weight loss did not change these relationships. CONCLUSIONS: The regulation of direct FFA storage under low FFA concentration conditions appears to be at the level of the cell/adipocyte content of CD36, whereas under high FFA concentration conditions, direct FFA storage at the tissue level is predicted by plasma FFA concentrations, independent of adipocyte size or fatty acid storage factors. These observations offer novel insights into how adipose tissue regulates direct FFA storage in humans.

Metabolic response 4 years after gastric bypass in a complete cohort with type 2 diabetes mellitus.

AIMS: To evaluate the long-term remission rates of type 2 diabetes mellitus and associated comorbidities after gastric bypass surgery in a complete cohort, in a real-life clinic setting. METHODS: A retrospective study of all consecutive patients with type 2 diabetes mellitus who underwent gastric bypass at a Veterans Affairs Medical Center from 2003 to 2010. The main outcome was remission of type 2 diabetes mellitus defined as HbA1c <6.5% (49 mmol/mol) without diabetic medication usage. Secondary outcomes were remission of hypertension and hyperlipidemia, weight loss, and long-term complications four years post-gastric bypass. RESULTS: Eighty-four patients with type 2 diabetes mellitus underwent gastric bypass. Four-year follow-up data were available for 92% (77/84) of patients. The patients (73% male; mean age 54 years) had a mean body mass index of 49 kg/m2 ±â€¯8.3. Hypertension and hyperlipidemia prevalence were 92% and 85%, respectively. The mean total body weight decrease over four years was 35 kg ±â€¯21. Remission of type 2 diabetes mellitus occurred in 15% at 6 months and 49% four years after surgery. Diabetes remission was more likely (OR 3.2; 95% confidence interval 1.2-9.7) in patients not using insulin at baseline. Remission rates were 12% (9/74) for hypertension and 16% (11/68) for hyperlipidemia. Long-term surgical complications included reoperation (11%), incisional hernia (10%) and anastomotic ulcer (10%). Forty-four percent of patients had one or more nutritional complications. CONCLUSIONS: The metabolic effects of gastric bypass are significant and durable for at least four years, even in a predominantly male cohort and real-life clinical setting.

Treatments to Prevent Bone Loss in Functional Hypothalamic Amenorrhea: A Systematic Review and Meta-Analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis of studies that evaluated the effect of hormonal therapy [estrogen therapy including oral contraceptive pills (OCP)] and bisphosphonates in preventing bone loss in patients with functional hypothalamic amenorrhea (FHA). METHODS: We searched several electronic databases for controlled and noncontrolled studies that enrolled females of any age presenting with FHA (including athletic, weight loss, and stress-associated amenorrhea/oligomenorrhea) through 9 January 2017. The outcomes of interest were fractures and bone mineral density (BMD). Random effects meta-analysis was used to pool outcomes across studies expressed as weighted mean difference and 95% confidence interval (CI). RESULTS: Nine studies reporting on 280 patients that received different hormonal therapies were included. We did not identify studies that evaluated bisphosphonates. Meta-analysis demonstrated a statistically significant increase in BMD of the lumbar spine in patients receiving hormonal therapy after a median follow-up of 12 months (weighted mean difference, 0.032 g/cm2; 95% CI, 0.017 to 0.047; percentage change in BMD, 3.30%; 95% CI, 1.74 to 4.86). There was no substantial effect of receiving hormonal therapy on BMD of the femoral neck, trochanteric region, Ward triangle, or total body BMD. The quality of evidence was low because of the high risk of bias, imprecision (small sample size), and indirectness (as BMD is a surrogate outcome). None of the studies reported the incidence of fractures. CONCLUSION: The current evidence does not support using hormonal therapy for the sole purpose of improving bone health in patients with FHA. There are no data about bisphosphonates in this population.

Comparison of Methods for Analyzing Human Adipose Tissue Macrophage Content.

OBJECTIVE: The relationship between inflammation, obesity, and adverse metabolic conditions is associated with adipose tissue macrophages (ATM). This study compared the measurements of human ATM using flow cytometry, immunohistochemistry (IHC), and real-time polymerase chain reaction (RT-PCR) of ATM markers. METHODS: A new software program (AMCounter) was evaluated to help measure ATM using IHC, and this was compared to flow cytometry and RT-PCR. RESULTS: IHC had good intraindividual reproducibility for total (CD68), proinflammatory (CD14), and anti-inflammatory (CD206) ATM. The AMCounter improved interreader agreement and was more time efficient. Flow cytometry had acceptable intraindividual reproducibility for the percentage of CD68+ cells that were CD14+ or CD206+ , but not for ATMs per gram of tissue. ATMs per gram of tissue was much greater using IHC than flow cytometry. The flow cytometry and IHC measures of ATM from the same biopsies were not correlated. There were statistically significant correlations between RT-PCR CD68 and IHC CD68, CD14, and CD206 ATMs per 100 adipocytes. Also of interest were statistically significant correlations between RT-PCR CD68 and IHC CD68, CD14, and adipose flow cytometry measures of CD68+ , CD68+ /CD14+ , and CD68+ /CD206+ ATMs per gram of tissue. CONCLUSIONS: The AMCounter software helps provide reproducible and efficient measures of IHC ATMs. Flow cytometry, IHC, and RT-PCR measures of adipose inflammation provide somewhat different information.

Thyroglobulin (Tg) Testing Revisited: Tg Assays, TgAb Assays, and Correlation of Results With Clinical Outcomes.

CONTEXT: Measurement of thyroglobulin (Tg) by mass spectrometry (Tg-MS) is emerging as a tool for accurate Tg quantification in patients with anti-Tg autoantibodies (TgAbs). OBJECTIVE: The objective of the study was to perform analytical and clinical evaluations of two Tg-MS assays in comparison with immunometric Tg assays (Tg-IAs) and Tg RIAs (Tg-RIAs) in a cohort of thyroid cancer patients. METHODS: A total of 589 samples from 495 patients, 243 TgAb-/252 TgAb+, were tested by Beckman, Roche, Siemens-Immulite, and Thermo-Brahms Tg and TgAb assays, two Tg-RIAs, and two Tg-MS assays. RESULTS: The frequency of TgAb+ was 58%, 41%, 27%, and 39% for Roche, Beckman, Siemens-Immulite, and Thermo-Brahms, respectively. In TgAb- samples, clinical sensitivities and specificities of 100% and 74%-100%, respectively, were observed across all assays. In TgAb+ samples, all Tg-IAs demonstrated assay-dependent Tg underestimation, ranging from 41% to 86%. In TgAb+ samples, the use of a common cutoff (0.5 ng/mL) for the Tg-MS, three Tg-IAs, and the USC-RIA improved the sensitivity for the Tg-MSs and Tg-RIAs when compared with the Tg-IAs. In up to 20% of TgAb+ cases, Tg-IAs failed to detect Tg that was detectable by Tg-MS. In Tg-RIAs false-high biases were observed in TgAb+ samples containing low Tg concentrations. CONCLUSIONS: Tg-IAs remain the method of choice for Tg quantitation in TgAb- patients. In TgAb+ patients with undetectable Tg by immunometric assay, the Tg-MS will detect Tg in up to 20% additional cases. The Tg-RIA will detect Tg in approximately 35% cases, but a significant proportion of these will be clinical false-positive results. The undetectable Tg-MS seen in approximately 40% of TgAb+ cases in patients with disease need further evaluation.