Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans.

A mysterious feature of Crohn's disease (CD) is the extra-intestinal manifestation of "creeping fat" (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria.

Differential effects of acute versus chronic dietary fructose consumption on metabolic responses in FVB/N mice.

Increased human consumption of high-fructose corn syrup has been linked to the marked increase in obesity and metabolic syndrome. Previous studies on the rapid effects of a high-fructose diet in mice have largely been confined to the C57BL/6 strains. In the current study, the FVB/N strain of mice that are resistant to diet-induced weight gain were used and fed a control or high-fructose diet for 48 h or for 12 wk. Many of the previously reported changes that occurred upon high-fructose feeding for 48 h in C57BL/6 mice were recapitulated in the FVB/N mice. However, the acute increases in fructolytic and lipogenic gene expression were completely lost during the 12-wk dietary intervention protocol. Furthermore, there was no significant weight gain in FVB/N mice fed a high-fructose diet for 12 wk, despite an overall increase in caloric consumption and an increase in average epididymal adipocyte cell size. These findings may be in part explained by a commensurate increase in energy expenditure and in carbohydrate utilization in high-fructose-fed animals. Overall, these findings demonstrate that FVB/N mice are a suitable model for the study of the effects of dietary intervention on metabolic and molecular parameters. Furthermore, the rapid changes in hepatic gene expression that have been widely reported were not sustained over a longer time course. Compensatory changes in energy expenditure and utilization may be in part responsible for the differences obtained between acute and chronic high-fructose feeding protocols.

Magnetic resonance angiography reveals increased arterial blood supply and tumorigenesis following high fat feeding in a mouse model of triple-negative breast cancer.

Breast cancer is the second most commonly diagnosed malignancy among women globally. Past MRI studies have linked a high animal fat diet (HAFD) to increased mammary cancer risk in the SV40Tag mouse model of triple-negative breast cancer. Here, serial MRI examines tumor progression and measures the arterial blood volume feeding mammary glands in low fat diet (LFD) or HAFD fed mice. Virgin female C3(1)SV40Tag mice (n = 8), weaned at 3 weeks old, were assigned to an LFD (n = 4, 3.7 kcal/g, 17.2% kcal from vegetable oil) or an HAFD (n = 4, 5.3 kcal/g, 60% kcal from lard) group. From ages 8 to 12 weeks, weekly fast spin echo MR images and time-of-flight (TOF) MR angiography of inguinal mammary glands were acquired at 9.4 T. Following in vivo MRI, mice were sacrificed. Inguinal mammary glands were excised and fixed for ex vivo MRI and histology. Tumor, blood, and mammary gland volumes for each time point were measured from manually traced regions of interest; tumors were classified as invasive by histopathology-blinded observers. Our analysis confirmed a strong correlation between total tumor volume and blood volume in the mammary gland. Tumor growth rates from weeks 8-12 were twice as high in HAFD-fed mice (0.42 ± 0.14/week) as in LFD-fed mice (0.21 ± 0.03/week), p < 0.004. Mammary gland blood volume growth rate was 2.2 times higher in HAFD mice (0.29 ± 0.11/week) compared with LFD mice (0.13 ± 0.06/week), p < 0.02. The mammary gland growth rate of HAFD-fed mice (0.071 ± 0.011/week) was 2.7 times larger than that of LFD-fed mice (0.026 ± 0.009/week), p < 0.01. This is the first non-invasive, in vivo MRI study to demonstrate a strong correlation between an HAFD and increased cancer burden and blood volume in mammary cancer without using contrast agents, strengthening the evidence supporting the adverse effects of an HAFD on mammary cancer. These results support the potential future use of TOF angiography to evaluate vasculature of suspicious lesions.

Effect of Needle Exchange Program on Maternal Hepatitis C Virus Prevalence.

OBJECTIVE: This study aimed to quantify the prevalence of maternal hepatitis C virus (HCV) before and after implementation of the needle exchange program (NEP) in Scioto County, Ohio. STUDY DESIGN: We conducted a population-based retrospective cohort study of all live births in Ohio (2006-2015). Frequency of maternal HCV was compared before (2006-2011) and after (2012-2015) the implementation of an NEP (2011) in Portsmouth, Ohio (Scioto County). Trends in maternal HCV prevalence in neighboring counties both physically adjacent and regional to Scioto County were also evaluated before and after NEP implementation. RESULTS: During the study period, there were 7,069 reported cases of maternal HCV infection at the time of delivery among 1,463,506 (0.5%) live births in Ohio. The rate of maternal HCV infection increased 137% in Scioto County between 2006 and 2011. After initiation of the NEP in Portsmouth, Ohio, in 2011, the rate of increase in the following 4 years (2012-2015) was 12%. The rate of increase in maternal HCV declined precipitously in counties physically adjacent to Scioto County, whereas regional counties continued to have substantial increases in maternal HCV. CONCLUSION: Rate of maternal HCV infection increased 137% versus 12% (rate difference: 125%) between pre- and post-NEP implementation time periods in Scioto County.

Psychosocial Stress Exposure Disrupts Mammary Gland Development.

Exposure to psychosocial stressors and ensuing stress physiology have been associated with spontaneous invasive mammary tumors in the Sprague-Dawley rat model of human breast cancer. Mammary gland (MG) development is a time when physiologic and environmental exposures influence breast cancer risk. However, the effect of psychosocial stress exposure on MG development remains unknown. Here, in the first comprehensive longitudinal study of MG development in nulliparous female rats (from puberty through young adulthood; 8-25 wks of age), we quantify the spatial gradient of differentiation within the MG of socially stressed (isolated) and control (grouped) rats. We then demonstrate that social isolation increased stress reactivity to everyday stressors, resulting in downregulation of glucocorticoid receptor (GR) expression in the MG epithelium. Surprisingly, given that chemical carcinogens increase MG cancer risk by preventing normal terminal end bud (TEB) differentiation, chronic isolation stress did not alter TEBs. Instead, isolation blunted MG growth and alveolobular differentiation and reduced epithelial cell proliferation in these structures. Social isolation also enhanced corpora luteal progesterone at all ages but reduced estrogenization only in early adulthood, a pattern that precludes modulated ovarian function as a sufficient mechanism for the effects of isolation on MG development. This longitudinal study of natural variation provides an integrated view of MG development and the importance of increased GR activation in nulliparous ductal growth and alveolobular differentiation. Thus, social isolation and its physiological sequelae disrupt MG growth and differentiation and suggest a contribution of stress exposure during puberty and young adulthood to the previously observed increase in invasive MG cancer observed in chronically socially-isolated adult Sprague-Dawley rats.

MRI reveals increased tumorigenesis following high fat feeding in a mouse model of triple-negative breast cancer.

High animal fat consumption is associated with an increase in triple-negative breast cancer (TNBC) risk. Based on previous MRI studies demonstrating the feasibility of detecting very early non-palpable mammary cancers in simian virus 40 large T antigen (SV40TAg) mice, we examined the effect of dietary fat fed from weaning to young adulthood in this model of TNBC. Virgin female C3(1)SV40TAg mice (n = 16) were weaned at 3-4 weeks of age and then fed either a low fat diet (LFD) (n = 8, 3.7 kcal/g; 17.2% kcal from vegetable oil) or a high animal fat diet (HAFD) (n = 8, 5.3 kcal/g; 60% kcal from lard). After 8 weeks on the diet (12 weeks of age), fast spin echo MR images of inguinal mammary glands were acquired at 9.4 T. Following in vivo MRI, mice were sacrificed and inguinal mammary glands were excised and formalin fixed for ex vivo MRI. 3D volume-rendered MR images were then correlated with mammary gland histology to assess the glandular parenchyma and tumor burden. Using in vivo MRI, an average of 3.88 ± 1.03 tumors were detected per HAFD-fed mouse compared with an average of 1.25 ± 1.16 per LFD-fed mouse (p < 0.007). Additionally, the average tumor volume was significantly higher following HAFD feeding (0.53 ± 0.45 mm3 ) compared with LFD feeding (0.20 ± 0.08 mm3 , p < 0.02). Analysis of ex vivo MR and histology images demonstrated that HAFD mouse mammary glands had denser parenchyma, irregular and enlarged ducts, dilated blood vessels, increased white adipose tissue, and increased tumor invasion. MRI and histological studies of the SV40TAg mice demonstrated that HAFD feeding also resulted in higher cancer incidence and larger mammary tumors. Unlike other imaging methods for assessing environmental effects on mammary cancer growth, MRI allows routine serial measurements and reliable detection of small cancers as well as accurate tumor volume measurements and assessment of the three-dimensional distribution of tumors over time.

Peripheral circadian misalignment: contributor to systemic insulin resistance and potential intervention to improve bariatric surgical outcomes.

Thirteen percent of the world's population suffers from obesity and 39% from being overweight, which correlates with an increase in numerous secondary metabolic complications, such as Type 2 diabetes mellitus. Bariatric surgery is the most effective treatment for severe obesity and results in significant weight loss and the amelioration of obesity-related comorbidities through changes in enteroendocrine activity, caloric intake, and alterations in gut microbiota composition. The circadian system has recently been found to be a critical regulatory component in the control of metabolism and, thus, may potentially play an important role in inappropriate weight gain. Indeed, some behaviors and lifestyle factors associated with an increased risk of obesity are also risk factors for misalignment in the circadian clock system and for the metabolic syndrome. It is thus possible that alterations in peripheral circadian clocks in metabolically relevant tissues are a contributor to the current obesity epidemic. As such, it is plausible that postsurgical alterations in central circadian alignment, as well as peripheral gene expression in metabolic tissues may represent another mechanism for the beneficial effects of bariatric surgery. Bariatric surgery may represent an opportunity to identify changes in the circadian expression of clock genes that have been altered by environmental factors, allowing for a better understanding of the mechanism of action of surgery. These studies could also reveal an overlooked target for behavioral intervention to improve metabolic outcomes following bariatric surgery.

Systemic regulation of adipose metabolism.

White adipose tissue serves as a critical energy storage depot and endocrine organ. Adipocytes are subject to numerous levels of regulation, including neuronal, endocrine and metabolic. While insulin is the classical endocrine regulator of lipid metabolism in adipose tissue, other important endocrine hormones also control adipose tissue physiology. In this review, we will focus on the contribution of the pituitary in the modulation of adipocyte function, through the direct release of growth hormone as well as via the regulation of the thyroid gland and release of thyroid hormone. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

The novel endocrine disruptor tolylfluanid impairs insulin signaling in primary rodent and human adipocytes through a reduction in insulin receptor substrate-1 levels.

Emerging data suggest that environmental endocrine disrupting chemicals may contribute to the pathophysiology of obesity and diabetes. In a prior work, the phenylsulfamide fungicide tolylfluanid (TF) was shown to augment adipocyte differentiation, yet its effects on mature adipocyte metabolism remain unknown. Because of the central role of adipose tissue in global energy regulation, the present study tested the hypothesis that TF modulates insulin action in primary rodent and human adipocytes. Alterations in insulin signaling in primary mammalian adipocytes were determined by the phosphorylation of Akt, a critical insulin signaling intermediate. Treatment of primary murine adipose tissue in vitro with 100nM TF for 48h markedly attenuated acute insulin-stimulated Akt phosphorylation in a strain- and species-independent fashion. Perigonadal, perirenal, and mesenteric fat were all sensitive to TF-induced insulin resistance. A similar TF-induced reduction in insulin-stimulated Akt phosphorylation was observed in primary human subcutaneous adipose tissue. TF treatment led to a potent and specific reduction in insulin receptor substrate-1 (IRS-1) mRNA and protein levels, a key upstream mediator of insulin's diverse metabolic effects. In contrast, insulin receptor-ß, phosphatidylinositol 3-kinase, and Akt expression were unchanged, indicating a specific abrogation of insulin signaling. Additionally, TF-treated adipocytes exhibited altered endocrine function with a reduction in both basal and insulin-stimulated leptin secretion. These studies demonstrate that TF induces cellular insulin resistance in primary murine and human adipocytes through a reduction of IRS-1 expression and protein stability, raising concern about the potential for this fungicide to disrupt metabolism and thereby contribute to the pathogenesis of diabetes.

Impaired insulin signaling in human adipocytes after experimental sleep restriction: a randomized, crossover study.

BACKGROUND: Insufficient sleep increases the risk for insulin resistance, type 2 diabetes, and obesity, suggesting that sleep restriction may impair peripheral metabolic pathways. Yet, a direct link between sleep restriction and alterations in molecular metabolic pathways in any peripheral human tissue has not been shown. OBJECTIVE: To determine whether sleep restriction results in reduced insulin sensitivity in subcutaneous fat, a peripheral tissue that plays a pivotal role in energy metabolism and balance. DESIGN: Randomized, 2-period, 2-condition, crossover clinical study. SETTING: University of Chicago Clinical Resource Center. PARTICIPANTS: Seven healthy adults (1 woman, 6 men) with a mean age of 23.7 years (SD, 3.8) and mean body mass index of 22.8 kg/m(2) (SD, 1.6). INTERVENTION: Four days of 4.5 hours in bed or 8.5 hours in bed under controlled conditions of caloric intake and physical activity. MEASUREMENTS: Adipocytes collected from subcutaneous fat biopsy samples after normal and restricted sleep conditions were exposed to incremental insulin concentrations. The ability of insulin to increase levels of phosphorylated Akt (pAkt), a crucial step in the insulin-signaling pathway, was assessed. Total Akt (tAkt) served as a loading control. The insulin concentration for the half-maximal stimulation of the pAkt-tAkt ratio was used as a measure of cellular insulin sensitivity. Total body insulin sensitivity was assessed using a frequently sampled intravenous glucose tolerance test. RESULTS: The insulin concentration for the half-maximal pAkt-tAkt response was nearly 3-fold higher (mean, 0.71 nM [SD, 0.27] vs. 0.24 nM [SD, 0.24]; P = 0.01; mean difference, 0.47 nM [SD, 0.33]; P = 0.01), and the total area under the receiver-operating characteristic curve of the pAkt-tAkt response was 30% lower (P = 0.01) during sleep restriction than during normal sleep. A reduction in total body insulin sensitivity (P = 0.02) paralleled this impaired cellular insulin sensitivity. LIMITATION: This was a single-center study with a small sample size. CONCLUSION: Sleep restriction results in an insulin-resistant state in human adipocytes. Sleep may be an important regulator of energy metabolism in peripheral tissues. PRIMARY FUNDING SOURCE: National Institutes of Health.

Targeted expression of human vitamin D receptor in adipocytes decreases energy expenditure and induces obesity in mice.

Our previous studies demonstrated a high fat diet-resistant lean phenotype of vitamin D receptor (VDR)-null mutant mice mainly due to increased energy expenditure, suggesting an involvement of the VDR in energy metabolism. Here, we took a transgenic approach to further define the role of VDR in adipocyte biology. We used the aP2 gene promoter to target the expression of the human (h) VDR in adipocytes in mice. In contrast to the VDR-null mice, the aP2-hVDR Tg mice developed obesity compared with the wild-type counterparts without changes in food intake. The increase in fat mass was mainly due to markedly reduced energy expenditure, which was correlated with decreased locomotive activity and reduced fatty acid ß-oxidation and lipolysis in the adipose tissue in the transgenic mice. Consistently, the expression of genes involved in the regulation of fatty acid transport, thermogenesis, and lipolysis were suppressed in the transgenic mice. Taken together, these data confirm an important role of the VDR in the regulation of energy metabolism.

Late isocaloric eating increases hunger, decreases energy expenditure, and modifies metabolic pathways in adults with overweight and obesity.

Late eating has been linked to obesity risk. It is unclear whether this is caused by changes in hunger and appetite, energy expenditure, or both, and whether molecular pathways in adipose tissues are involved. Therefore, we conducted a randomized, controlled, crossover trial (ClinicalTrials.gov NCT02298790) to determine the effects of late versus early eating while rigorously controlling for nutrient intake, physical activity, sleep, and light exposure. Late eating increased hunger (p < 0.0001) and altered appetite-regulating hormones, increasing waketime and 24-h ghrelin:leptin ratio (p < 0.0001 and p = 0.006, respectively). Furthermore, late eating decreased waketime energy expenditure (p = 0.002) and 24-h core body temperature (p = 0.019). Adipose tissue gene expression analyses showed that late eating altered pathways involved in lipid metabolism, e.g., p38 MAPK signaling, TGF-ß signaling, modulation of receptor tyrosine kinases, and autophagy, in a direction consistent with decreased lipolysis/increased adipogenesis. These findings show converging mechanisms by which late eating may result in positive energy balance and increased obesity risk.

The silencing mediator of retinoid and thyroid hormone receptors (SMRT) regulates adipose tissue accumulation and adipocyte insulin sensitivity in vivo.

The silencing mediator of retinoid and thyroid hormone receptors (SMRT) serves as a corepressor for nuclear receptors and other factors. Recent evidence suggests that SMRT is an important regulator of metabolism, but its role in adipocyte function in vivo remains unclear. We generated heterozygous SMRT knock-out (SMRT(+/-)) mice to investigate the function of SMRT in the adipocyte and the regulation of adipocyte insulin sensitivity. We show that SMRT(+/-) mice are normal weight on a regular diet, but develop increased adiposity on a high-fat diet (HFD). The mechanisms underlying this phenotype are complex, but appear to be due to a combination of an increased number of smaller subcutaneous adipocytes as well as decreased leptin expression, resulting in greater caloric intake. In addition, adipogenesis of mouse embryonic fibroblasts (MEFs) derived from these mice was increased. However, adipocyte insulin sensitivity, measured by insulin-induced Akt phosphorylation and insulin-mediated suppression of lipolysis, was enhanced in SMRT(+/-) adipocytes. These finding suggest that SMRT regulates leptin expression and limits the ability of fat mass to expand with increased caloric intake, but that SMRT also negatively regulates adipocyte insulin sensitivity.

Insulin regulation of hepatic gluconeogenesis through phosphorylation of CREB-binding protein.

Hepatic gluconeogenesis is essential for maintenance of normal blood glucose concentrations and is regulated by opposing stimulatory (cyclic adenosine monophosphate, cAMP) and inhibitory (insulin) signaling pathways. The cAMP signaling pathway leads to phosphorylation of cAMP response element-binding (CREB) protein, resulting in recruitment of the coactivators CREB-binding protein (CBP) and p300 and subsequent activation of gluconeogenesis. Insulin signaling leads to phosphorylation of CBP at serine 436, a residue near its CREB-interacting domain, but it is unknown whether this event modulates cAMP signaling. Here, we show in vitro and in 'knock-in' mice that a mutant CBP (S436A) is aberrantly recruited to CREB protein, resulting in inappropriate activation of gluconeogenesis in the fed state and glucose intolerance resulting from increased hepatic glucose production. We propose that insulin signaling may directly regulate many cAMP signaling pathways at the transcriptional level by controlling CBP recruitment.

The Relationship between Sleep, Obesity, and Metabolic Health in Adolescents - a Review.

In this literature review, we discuss the importance of adequate sleep and the various effects of suboptimal sleep on weight maintenance and metabolic health specifically for adolescents. Two major contributors to adolescents experiencing decreased sleep duration and quality, and thus increasing the risk for developing metabolic syndrome in adolescence as well as later in adulthood, are increased electronic screen time particularly at night and early school start times. The less time adolescents spend sleeping, the less quality sleep they obtain, and the greater the disruption of endocrine hormone function. As another consequence, adolescents are more prone to making poor food choices, from choosing relatively nutrient-poor foods to consuming excess calories without necessarily increasing their energy expenditure. These choices put adolescents at greater risk for becoming obese throughout their lifespan.

Laminin-α4 Is Upregulated in Both Human and Murine Models of Obesity.

Obesity affects nearly one billion globally and can lead to life-threatening sequelae. Consequently, there is an urgent need for novel therapeutics. We have previously shown that laminin, alpha 4 (Lama4) knockout in mice leads to resistance to adipose tissue accumulation; however, the relationship between LAMA4 and obesity in humans has not been established. In this study we measured laminin-α chain and collagen mRNA expression in the subcutaneous white adipose tissue (sWAT) of mice placed on chow (RCD) or 45% high fat diet (HFD) for 8 weeks, and also in HFD mice then placed on a "weight loss" regimen (8 weeks HFD followed by 6 weeks RCD). To assess extracellular matrix (ECM) components in humans with obesity, laminin subunit alpha mRNA and protein expression was measured in sWAT biopsies of female control subjects (BMI<30) or subjects with obesity undergoing bariatric surgery at the University of Chicago Medical Center (BMI>35) both before and three months after surgery. Lama4 was significantly higher in sWAT of HFD compared to RCD mice at both the RNA and protein level (p<0.001, p<0.05 respectively). sWAT from human subjects with obesity also showed significantly higher LAMA4 mRNA (p<0.01) and LAMA4 protein expression (p<0.05) than controls. Interestingly, even though LAMA4 expression was increased in both humans and murine models of obesity, no significant difference in Lama4 or LAMA4 expression was detected following short-term weight loss in either mouse or human samples, respectively. From these results we propose a significant association between obesity and elevated LAMA4 expression in humans, as well as in mouse models of obesity. Further studies should clarify the mechanisms underlying this association to target LAMA4 effectively as a potential therapy for obesity.

Enhanced glycogen metabolism in adipose tissue decreases triglyceride mobilization.

Adipose tissue is a primary site for lipid storage containing trace amounts of glycogen. However, refeeding after a prolonged partial fast produces a marked transient spike in adipose glycogen, which dissipates in coordination with the initiation of lipid resynthesis. To further study the potential interplay between glycogen and lipid metabolism in adipose tissue, the aP2-PTG transgenic mouse line was utilized since it contains a 100- to 400-fold elevation of adipocyte glycogen levels that are mobilized upon fasting. To determine the fate of the released glucose 1-phosphate, a series of metabolic measurements were made. Basal and isoproterenol-stimulated lactate production in vitro was significantly increased in adipose tissue from transgenic animals. In parallel, basal and isoproterenol-induced release of nonesterified fatty acids (NEFAs) was significantly reduced in transgenic adipose tissue vs. control. Interestingly, glycerol release was unchanged between the genotypes, suggesting that enhanced triglyceride resynthesis was occurring in the transgenic tissue. Qualitatively similar results for NEFA and glycerol levels between wild-type and transgenic animals were obtained in vivo during fasting. Additionally, the physiological upregulation of the phosphoenolpyruvate carboxykinase cytosolic isoform (PEPCK-C) expression in adipose upon fasting was significantly blunted in transgenic mice. No changes in whole body metabolism were detected through indirect calorimetry. Yet weight loss following a weight gain/loss protocol was significantly impeded in the transgenic animals, indicating a further impairment in triglyceride mobilization. Cumulatively, these results support the notion that the adipocyte possesses a set point for glycogen, which is altered in response to nutritional cues, enabling the coordination of adipose glycogen turnover with lipid metabolism.

Making fat work.

The burgeoning obesity and metabolic disease epidemics in the developed world are exerting a terrible toll on society, yet the precise mechanisms responsible for the emergence of these dramatic trends over a relatively short period of time remain poorly understood. Philip A.Wood's book How Fat Works provides important insights into cellular lipid metabolism, as well as discussing some of the important external contributors to the development of human obesity. The foundation provided by this book allows for the exploration of how body fat has gone from hero during the millennia when starvation was the paramount nutritional risk to its current role as villain in our period of caloric excess. With the incredible personal and societal costs brought about by excess body weight, a comprehensive understanding of the mechanisms responsible for obesity is fundamentally necessary if we are to reverse these dire trends. Here, we delve deeper into some of the forces contributing to the obesity epidemic and discuss some individual measures as well as public policy decisions that may help reverse weight trends, while specifically focusing on the growing problem of pediatric obesity.

Reduction of IL-6 gene expression in human adipose tissue after sleeve gastrectomy surgery.

OBJECTIVE: There is increasing evidence that immune cell interactions in adipose tissue contribute to the development of metabolic dysfunction. Pro-inflammatory cytokines have been shown to mediate insulin resistance, and the presence of macrophages is a salient feature in the development of obesity. The present study aimed to evaluate adipocyte size and macrophage activation in women before and 3 months after laparoscopic vertical sleeve gastrectomy (VSG). METHODS: Subcutaneous abdominal adipose tissue biopsies were obtained from women scheduled to undergo VSG. Histological evaluation of adipocytes and macrophages was performed as well as cytokine expression quantification before and after VSG-induced weight loss. RESULTS: Weight loss following VSG resulted in a reduction in adipocyte size as well as a decrease in interleukin (IL)-6 cytokine mRNA expression in subcutaneous adipose tissue. There was no change in the presence of crownlike structures after weight loss. CONCLUSIONS: Early weight loss after VSG is associated with a reduction in adipocyte size and a decline in IL-6 gene expression in local adipose tissue. Macrophage infiltration and crownlike density structures persist in adipose tissue from tissues impacted by excess body weight 3 months after VSG-induced weight loss.