We sought to assess whether direct uptake of circulating free fatty acids (FFAs) by adipocytes occurs in vivo in overnight postabsorptive humans and, if so, whether there are regional differences in uptake between lean and obese women and men. We used bolus injections of radiolabeled FFA tracers followed by carefully timed adipose tissue biopsies. First, we validated a method to measure direct adipocyte FFA uptake and then quantitated this process using the modified methods in normalweight postabsorptive men and women. We then used a continuous infusion of radiolabeled FFA to measure direct and indirect (VLDL) regional adipose tissue uptake in obese men and women. Direct FFA uptake was greater in women than men: 8.2 ؎ 0.6 vs. 4.0 ؎ 0.5% (P < 0.0001) of FFAs were taken up by subcutaneous adipose tissue, respectively. Abdominal subcutaneous fat took up FFAs more avidly than femoral fat in men, but this did not occur in women. Similar sex and regional difference were found to occur in obese women and men. Gene expression of fatty acid transporters was greater in abdominal than femoral fat in men (P < 0.05) but not in women (P ‫؍‬ 0.80). We observed sex-and site-specific recycling of circulating FFAs into subcutaneous fat. This is a novel FFA disposal pathway that may also play a role in the development or maintenance of body fat distribution. Regional variations in facilitated fatty acid transport may contribute to this process. Diabetes 56:1369-1375, 2007

We hypothesized that plasma non-esterified fatty acids (NEFA) are trafficked directly to intramyocellular long-chain acylcarnitines (imLCAC) rather than transiting intramyocellular triglycerides (imTG) on the way to resting muscle fatty acid oxidation. Overnight fasted adults (n = 61) received intravenous infusions of [U-13 C]palmitate (0400-0830 h) and [U-13 C]oleate (0800-1400 h) labelling plasma NEFA, imTG, imLCAC and im-non-esterified FA (imNEFA). Two muscle biopsies (0830 and 1400 h) were performed following 6 h, overlapping, sequential palmitate/oleate tracer infusions. Enrichment of plasma palmitate was ∼15 times greater than enrichment of imTG, imNEFA-palmitate and im-palmitoyl-carnitine. Fatty acid enrichment in LCAC was correlated with imTG and imNEFA; there was a significant correlation between imTG concentrations and imLCAC concentrations in women (r = 0.51, P = 0.005), but not men (r = 0.30, P = 0.11). We estimated that ∼11% of NEFA were stored in imTG. imTG NEFA storage was correlated only with NEFA concentrations (r = 0.52, P = 0.004) in women and witḣ V O 2 ,peak (r = 0.45, P = 0.02) in men. At rest, plasma NEFA are trafficked largely to imTG before they enter LCAC oxidative pools; thus, imTG are an important, central pool that regulates the delivery of fatty acids to the intracellular environment. Factors relating to plasma NEFA storage into imTG differ in men and women.

OBJECTIVE -Insulin resistance is associated with visceral adiposity, and interventions that reduce this depot, e.g., diet and exercise, improve insulin resistance. Thiazolidinediones (TZDs) also improve insulin action but paradoxically increase total fat mass, perhaps through remodeling (recruitment of smaller fat cells) and redistribution of adipose tissue. We assessed the effects of pioglitazone versus diet and exercise on fat distribution and the relationship between fat distribution and insulin sensitivity in upper body obesity.RESEARCH DESIGN AND METHODS -Thirty-nine upper body obese, insulinresistant, nondiabetic men and premenopausal women were randomly assigned to receive either 30 mg/day pioglitazone or a diet and exercise program for 20 weeks. Before and after the intervention, insulin sensitivity, body composition, body fat distribution (waist-to-hip ratio [WHR], computed tomography abdomen, and dual-energy X-ray absorptiometry), and abdominal and femoral fat cell size were assessed.RESULTS -Diet and exercise resulted in an 11.8 Ϯ 1.1 kg weight loss. Both diet and exercise and pioglitazone improved insulin sensitivity, but only the former was associated with loss of intra-abdominal fat. Pioglitazone increased total body fat, which preferentially accumulated in the lower body depot in both men and women. WHRs decreased in both groups. Abdominal fat cell size decreased (P ϭ 0.06) after diet and exercise. No statistically significant changes in fat cell size were observed in pioglitazone-treated volunteers.CONCLUSIONS -In nondiabetic upper body obese subjects, increasing insulin sensitivity via diet and exercise accompanies reductions in visceral fat. Pioglitazone treatment also improves insulin sensitivity and lowers WHR, but this is due to a selective increase in lower body fat. This confirms a site-specific responsiveness of adipose tissue to TZD and suggests that improvements in insulin sensitivity by pioglitazone are achieved independent of changes in intra-abdominal fat. Diabetes Care 26:3148 -3152, 2003B ody fat distribution is an important variable in the relationship between overweight and insulin resistance. Intra-abdominal or visceral fat accumulation is more strongly associated with insulin resistance, and insulin resistance can be improved by decreasing this fat depot via diet, exercise, or surgery (1,2). Thiazolidinediones (TZDs) are also known to improve insulin sensitivity despite paradoxically increasing total fat mass (3-5). It has been suggested that redistribution of body fat may contribute to their insulin-sensitizing qualities. Indeed, regional variability in TZD responsiveness has been demonstrated; preadipocytes from subcutaneous fat differentiate more in response to TZD in vitro than visceral adipose tissue (6). If the same phenomenon occurs in vivo, one would expect selective adipocyte proliferation and thus body fat redistribution.However, studies of animals and diabetic humans have reported increasing, decreasing, and unchanged visceral and subcutaneous fat depots after TZD ad...

Background Adopting an active lifestyle plays a key role in the prevention and management of chronic diseases such as type 2 diabetes mellitus (T2DM). Web-based interventions are able to alter health behaviors and show stronger effects when they are informed by a behavior change theory. MyPlan 2.0 is a fully automated electronic health (eHealth) and mobile health (mHealth) intervention targeting physical activity (PA) and sedentary behavior (SB) based on the Health Action Process Approach (HAPA). Objective This study aimed to test the short-term effect of MyPlan 2.0 in altering levels of PA and SB and in changing personal determinants of behavior in adults with T2DM and in adults aged ≥50 years. Methods The study comprised two randomized controlled trials (RCTs) with an identical design. RCT 1 was conducted with adults with T2DM. RCT 2 was performed in adults aged ≥50 years. Data were collected via face-to-face assessments. The participants decided either to increase their level of PA or to decrease their level of SB. The participants were randomly allocated with a 2:1 ratio to the intervention group or the waiting-list control group. They were not blinded for their group allocation. The participants in the intervention group were instructed to go through MyPlan 2.0, comprising 5 sessions with an interval of 1 week between each session. The primary outcomes were objectively measured and self-reported PA (ie, light PA, moderate-to-vigorous PA, total PA, number of steps, and domain-specific [eg, transport-related] PA) and SB (ie, sitting time, number of breaks from sitting time, and length of sitting bouts). Secondary outcomes were self-reported behavioral determinants for PA and SB (eg, self-efficacy). Separate linear mixed models were performed to analyze the effects of MyPlan 2.0 in the two samples. Results In RCT 1 (n=54), the PA intervention group showed, in contrast to the control group, a decrease in self-reported time spent sitting (P=.09) and an increase in accelerometer-measured moderate (P=.05) and moderate-to-vigorous PA (P=.049). The SB intervention group displayed an increase in accelerometer-assessed breaks from sedentary time in comparison with the control group (P=.005). A total of 14 participants of RCT 1 dropped out. In RCT 2 (n=63), the PA intervention group showed an increase for self-reported total PA in comparison with the control group (P=.003). Furthermore, in contrast to the control group, the SB intervention group decreased their self-reported time spent sitting (P=.08) and increased their accelerometer-assessed moderate (P=.06) and moderate-to-vigorous PA (P=.07). A total of 8 participants of RCT 2 dropped out. Conclusions For both the samples, the HAPA-based eHealth and mHealth intervention, MyPlan 2.0, was able to improve only some of the primary outcomes. Trial Registration ClinicalTrials.gov NCT03291171; http://clinicaltrials.gov/ct2/show/NCT03291171. ClinicalTrials.gov NCT03799146; http://clinicaltrials.gov/ct2/show/NCT03799146. International Registered Report Identifier (IRRID) RR2-10.2196/12413

The long-term influences of sex hormone administration on insulin sensitivity and incretin hormones are controversial. We investigated these effects in 35 transgender men (TM) and 55 transgender women (TW) from the European Network for the Investigation of Gender Incongruence (ENIGI) study. RESEARCH DESIGN AND METHODSBefore and after 1 year of gender-affirming hormone therapy, body composition and oral glucose tolerance tests (OGTTs) were evaluated. RESULTSIn TM, body weight (2.8 6 1.0 kg; P < 0.01), fat-free mass (FFM) (3.1 6 0.9 kg; P < 0.01), and waist-to-hip ratio (20.03 6 0.01; P < 0.01) increased. Fasting insulin (21.4 6 0.8 mU/L; P 5 0.08) and HOMA of insulin resistance (HOMA-IR) (2.2 6 0.3 vs. 1.8 6 0.2; P 5 0.06) tended to decrease, whereas fasting glucose (21.6 6 1.6 mg/dL), glucose-dependent insulinotropic polypeptide (GIP) (21.8 6 1.0 pmol/L), and glucagon-like peptide 1 (GLP-1) (20.2 6 1.1 pmol/L) were statistically unchanged. Post-OGTT areas under the curve (AUCs) for GIP (2,068 6 1,134 vs. 2,645 6 1,248 [pmol/L] 3 min; P < 0.01) and GLP-1 (2,352 6 796 vs. 2,712 6 1,015 [pmol/L] 3 min; P < 0.01) increased. In TW, body weight tended to increase (1.4 6 0.8 kg; P 5 0.07) with decreasing FFM (22.3 6 0.4 kg; P < 0.01) and waist-to-hip ratio (20.03 6 0.01;