Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFehi, and the remaining ATMs are referred to as MFelo. In lean mice, ~25% of the ATMs are MFehi; this percentage decreases in obesity owing to the recruitment of MFelo macrophages. Similar to MFelo cells, MFehi ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFehi ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFehi iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFehi ATM phenotype and their reduced capacity to handle iron.

Abstract-We tested the hypothesis that weight loss via a hypocaloric diet would reduce arterial stiffness in overweight and obese middle-aged and older adults. Thirty-six individuals were randomly assigned to a weight loss (nϭ25; age: 61.2Ϯ0.8 years; body mass index: 30.0Ϯ0.6 kg/m 2 ) or a control (nϭ11; age: 66.1Ϯ1.9 years; body mass index: 31.8Ϯ1.4 kg/m 2 ) group. Arterial stiffness was measured via carotid artery ultrasonography combined with applanation tonometry and carotid-femoral pulse wave velocity via applanation tonometry at baseline and after the 12-week intervention. Body weight, body fat, abdominal adiposity, blood pressure, ␤-stiffness index, and carotid-femoral pulse wave velocity were similar in the 2 groups at baseline (all PϾ0.05). Body weight (Ϫ7.1Ϯ0.7 versus Ϫ0.7Ϯ1.1 kg), body fat, and abdominal adiposity decreased in the weight loss group but not in the control group (all PϽ0.05). Brachial systolic and diastolic blood pressures declined (PϽ0.05) only in the weight loss group. Central systolic and pulse pressures did not change significantly in either group. ␤-Stiffness index (Ϫ1.24Ϯ0.22 versus 0.52Ϯ0.37 U) and carotid-femoral pulse wave velocity (Ϫ187Ϯ29 versus 15Ϯ42 cm/s) decreased in the weight loss group but not in the control group (all PϽ0.05). The reductions in carotid-femoral pulse wave velocity were correlated with reductions in total body and abdominal adiposity (rϭ0. all PϽ0.05). However, neither total body nor abdominal adiposity independently predicted reductions in arterial stiffness indices. In summary, our findings indicate that weight loss reduces arterial stiffness in overweight/obese middle-aged and older adults, and the magnitudes of these improvements are related to the loss of total and abdominal adiposity.

The sympathetic nervous system (SNS) plays an essential role in the regulation of metabolic and cardiovascular homeostasis. Low SNS activity has been suggested to be a risk factor for weight gain and obesity development. In contrast, SNS activation is characteristic of a number of metabolic and cardiovascular diseases that occur more frequently in obese individuals. Until recently, the relation between obesity and SNS behavior has been controversial because previous approaches for assessing SNS activity in humans have produced inconsistent findings. Beginning in the early 1990's, many studies using state of the art neurochemical and neurophysiological techniques have provided important insight. The purpose of the present review is to provide an overview of our current understanding of the regional specific alterations in SNS behavior in human obesity. We will discuss findings from our own laboratory which implicate visceral fat as an important depot linking obesity with skeletal muscle SNS activation. The influence of weight change on SNS behavior and the potential mechanisms and consequences of region specific SNS activation in obesity will also be considered.

Obesity is characterized by adipose tissue (AT) macrophage (ATM) accumulation, which promotes AT inflammation and dysfunction. Toll-like receptor 4 (TLR4) deficiency attenuates AT inflammation in obesity but does not impede the accumulation of ATMs. The purpose of the current study was to determine whether TLR4 deficiency alters ATM polarization. TLR4−/− and wild-type mice were fed a low-fat, high-monounsaturated fat (HFMUFA), or a high-saturated fat (HFSFA) diet for 16 weeks. Further, we used a bone marrow transplant model to determine the influence of hematopoietic cell TLR4 signaling. The metabolic and inflammatory responses to high-fat feeding and ATM phenotype were assessed. Global and hematopoietic cell TLR4 deficiency, irrespective of recipient genotype, produced a shift in ATM phenotype toward an alternatively activated state, which was accompanied by reduced AT inflammation. Despite the observed shift in ATM phenotype, neither global nor hematopoietic cell TLR4 deficiency influenced systemic insulin sensitivity after high-fat feeding. Results of the current study suggest that TLR4 directly influences ATM polarization but question the relevance of TLR4 signaling to systemic glucose homeostasis in obesity.

Background: Energy intake (EI) regulation is impaired in older adults, but it is not known if habitual physical activity affects accuracy of EI regulation in older compared with young adults. Objective: We hypothesized that the ability to compensate for a high-energy yogurt preload beverage at a subsequent ad libitum meal (i.e. acute compensation) and over the course of the testing day (i.e. short-term compensation) would decrease with age, but the magnitude of the decline would be smaller in physically active compared with sedentary older adults. Design: On two occasions, young active (n ¼ 15), young sedentary (n ¼ 14), older active (n ¼ 14) and older sedentary (n ¼ 11) subjects consumed either a high-energy yogurt preload beverage (YP: 500 ml, 1988 kJ, men; 375 ml, 1507 kJ, women), or no preload (NP), 30 min before an ad libitum test meal. EI at both ad libitum meals was measured, and total daily EI was determined on both testing days. Percent EI compensation for the YP was calculated for the test meal and testing day to determine acute and short-term compensation. Results: Percent EI compensation at the test meal was significantly lower in the older compared with the young subjects (6574 vs 8174%, P ¼ 0.005). There was no effect of habitual physical activity level on acute compensation, and no age by physical activity level interaction (P ¼ 0.60). In contrast, short-term compensation was not different with age (8775 vs 9376%, older vs young, P ¼ 0.45), but was more accurate in active vs sedentary subjects (10075 vs 7976%, P ¼ 0.01). As with acute compensation, there was no age by physical activity interaction (P ¼ 0.39). Conclusion: Acute EI regulation is impaired in older adults, which is not attenuated by physical activity status. However, EI regulation over the course of a day is more accurate in active vs sedentary adults, which may facilitate long-term energy balance. Future work is needed to determine if higher energy expenditure in older active vs older sedentary adults improves long-term EI regulation.