Obesity-induced Changes Research Articles

The Virtual Hand Illusion in Obesity: Dissociation Between Multisensory Interactions Supporting Illusory Experience and Self-Location Recalibration.

The Rubber Hand Illusion (RHI) is used widely to investigate the multisensory integration mechanisms that support bodily self-consciousness and, more specifically, body ownership and self-location. It has been reported that individuals affected by obesity show anomalous multisensory integration processes. We propose that these obesity-induced changes could lead to an unusual susceptibility to the RHI and anomalous bodily self-experience. To test this hypothesis, we administered a modified version of the RHI (using a picture of the participant's hand) to individuals affected by obesity and participants with a healthy weight. During synchronous and asynchronous stimulation, we compared the subjective experience of the illusion (using a questionnaire) and the effect of the illusion on self-location (i.e., proprioceptive drift). In accordance with the illusion phenomenology, both groups had a comparable subjective illusory experience after the synchronous stimulation. Nevertheless, individuals affected by obesity showed less recalibration of self-location than healthy weight participants. In light of a recent interpretation of the multisensory integration mechanisms that underpin the RHI, our findings suggest that in obesity visuo-tactile integration supporting the subjective experience of the illusion is preserved, whereas visuo-proprioceptive integration for self-location is reduced.

Weighing the Risk: effects of Obesity on the Mammary Gland and Breast Cancer Risk.

Obesity is a preventable risk factor for breast cancer following menopause. Regardless of menopausal status, obese women who develop breast cancer have a worsened prognosis. Breast tissue is comprised of mammary epithelial cells organized into ducts and lobules and surrounded by adipose-rich connective tissue. Studies utilizing multiple in vivo models of obesity as well as human breast tissue have contributed to our understanding of how obesity alters mammary tissue. Localized changes in mammary epithelial cell populations, elevated secretion of adipokines and angiogenic mediators, inflammation within mammary adipose tissue, and remodeling of the extracellular matrix may result in an environment conducive to breast cancer growth. Despite these significant alterations caused by obesity within breast tissue, studies have suggested that some, but not all, obesity-induced changes may be mitigated with weight loss. Here, we review our current understanding regarding the impact of obesity on the breast microenvironment, how obesity-induced changes may contribute to breast tumor progression, and the impact of weight loss on the breast microenvironment.

Regulation of Lymphatic Function in Obesity.

The lymphatic system has many functions, including macromolecules transport, fat absorption, regulation and modulation of adaptive immune responses, clearance of inflammatory cytokines, and cholesterol metabolism. Thus, it is evident that lymphatic function can play a key role in the regulation of a wide array of biologic phenomenon, and that physiologic changes that alter lymphatic function may have profound pathologic effects. Recent studies have shown that obesity can markedly impair lymphatic function. Obesity-induced pathologic changes in the lymphatic system result, at least in part, from the accumulation of inflammatory cells around lymphatic vessel leading to impaired lymphatic collecting vessel pumping capacity, leaky initial and collecting lymphatics, alterations in lymphatic endothelial cell (LEC) gene expression, and degradation of junctional proteins. These changes are important since impaired lymphatic function in obesity may contribute to the pathology of obesity in other organ systems in a feed-forward manner by increasing low-grade tissue inflammation and the accumulation of inflammatory cytokines. More importantly, recent studies have suggested that interventions that inhibit inflammatory responses, either pharmacologically or by lifestyle modifications such as aerobic exercise and weight loss, improve lymphatic function and metabolic parameters in obese mice. The purpose of this review is to summarize the pathologic effects of obesity on the lymphatic system, the cellular mechanisms that regulate these responses, the effects of impaired lymphatic function on metabolic syndrome in obesity, and the interventions that may improve lymphatic function in obesity.

Obesity-Induced Changes in Bone Marrow Homeostasis.

Obesity is characterized by low-grade inflammation, which is accompanied by increased accumulation of immune cells in peripheral tissues including adipose tissue (AT), skeletal muscle, liver and pancreas, thereby impairing their primary metabolic functions in the regulation of glucose homeostasis. Obesity has also shown to have a detrimental effect on bone homeostasis by altering bone marrow and hematopoietic stem cell differentiation and thus impairing bone integrity and immune cell properties. The origin of immune cells arises in the bone marrow, which has been shown to be affected with the obesogenic condition via increased cellularity and shifting differentiation and function of hematopoietic and bone marrow mesenchymal stem cells in favor of myeloid progenitors and increased bone marrow adiposity. These obesity-induced changes in the bone marrow microenvironment lead to dramatic bone marrow remodeling and compromising immune cell functions, which in turn affect systemic inflammatory conditions and regulation of whole-body metabolism. However, there is limited information on the inflammatory secretory factors creating the bone marrow microenvironment and how these factors changed during metabolic complications. This review summarizes recent findings on inflammatory and cellular changes in the bone marrow in relation to obesity and further discuss whether dietary intervention or physical activity may have beneficial effects on the bone marrow microenvironment and whole-body metabolism.

Obesity Might Persistently Increase Adrenal Gland Volume: a Preliminary Study.

This study aimed to investigate the association of obesity with adrenal gland volume (AGV) and the effects of weight loss on AGV. This study included obese patients (N = 25) who underwent sleeve gastrectomy and age- and sex-matched healthy volunteers (HVs) (N = 25) and overweight healthy volunteers (overweight-HVs) (N = 21). Thin-slice computed tomography was used to evaluate adrenal morphological changes. AGV was measured semiautomatically based on the digital imaging and communications in medicine (DICOM) image. The effects of weight loss on AGV and adrenal gland density were evaluated in patients for 1year or more after sleeve gastrectomy. Left, right, and total AGV were 6.77 ± 0.36, 5.76 ± 0.31, and 12.53 ± 0.64cm3 in obese patients, which were significantly higher than those in the overweight-HVs (3.88 ± 0.14, 3.09 ± 0.13, and 6.97 ± 0.24cm3) and HVs (3.38 ± 0.23, 2.67 ± 0.15, and 6.04 ± 0.36cm3). AGV was larger in overweight-HVs than in HVs, but no statistically significant difference was identified. Sleeve gastrectomy significantly reduced body weight (- 27.1 ± 2.5kg), left AGV (- 0.80 ± 0.26cm3), and right AGV (- 0.88 ± 0.20cm2). The adrenal volume in five patients was not reduced, despite significant weight loss postsurgery. The mean density of adrenal glands was lower in obese patients (P = 0.025) but were not significantly increased postsurgery. Obesity leads to increased AGV, and in some cases, this effect seems to be irreversible. The clinical implication of obesity-induced adrenal morphological changes needs to be studied further.

Obesity alters the immune landscape of the small intestine and exacerbates food allergy

Abstract In the past few decades, higher rates of obesity have coincided with a rising number of individuals affected by allergic disease. Our study objective was to determine if obesity alters the immune cell landscape of the small intestine towards an inflammatory environment that aggravates the development of food allergy. Obesity was induced by feeding male BALB/c mice a western diet for 8 weeks. To induce food allergy, mice were epicutaneously sensitized and orally-challenged with OVA. Compared with lean controls, sensitized obese mice showed a lower body temperature after challenge and increased OVA-specific IgE in serum, suggesting an exacerbated allergic response. Mass cytometry analysis of the intestinal lamina propria revealed that OVA-sensitized obese mice had decreased T regulatory cells, which are critical for the oral tolerance to food allergens. In the mesenteric lymph node, obese mice showed increased frequencies of T follicular helper cells (Tfh) compared with lean controls. Tfh cells are required for the production of allergen-specific IgE, and implicated in allergic disease pathogenesis. To further define the transcriptional mechanisms underpinning the increased inflammatory and allergic responses during obesity, we performed single-cell RNA sequencing of more than 28,000 barcoded CD45+ enriched lamina propria cells from lean and obese mice, with and without OVA sensitization. We provide a transcriptional map of inflammatory cells and define a module of gene expression that distinguishes immune cell-driven allergic responses in the obese intestine. Overall, our findings highlight obesity-induced inflammatory changes in the intestine that may mediate the increased food allergic sensitization during obesity.

Hepatocyte HIF‐1alpha mediates obesity‐induced decreased incretin effects

The decrease in incretin effects is an important etiologic component of type 2 diabetes with unknown mechanisms. In an attempt to understand obesity‐induced changes in liver oxygen homeostasis and its metabolic consequence, we came across a novel finding that liver HIF‐1α expression was increased mainly by soluble factors released from obese adipocytes, leading to decreased incretin effects. In‐depth mouse metabolic phenotyping revealed that obesity increased first‐pass degradation of an incretin hormone GLP‐1 with increased liver DPP4 expression and decreased sinusoidal blood flow rate, reducing active GLP‐1 levels in peripheral circulation. Deletion of hepatocyte HIF‐1α KO blocked these changes induced by obesity: hepatocyte HIF‐1α KO mice were protected from obesity‐induced glucose intolerance without changes in body weight, liver steatosis, or insulin resistance. Deletion of hepatocyte HIF‐2α did not change liver DPP4 expression but improved hepatic steatosis. Our results identify a previously unknown pathway for obesity‐induced impaired beta cell glucose response (incretin effects) and the development of glucose intolerance through inter‐organ communications.

1033: Obesity-induced epigenetic changes associated with adverse perinatal outcomes

Maternal obesity is associated with higher risk of fetal/neonatal mortality and morbidity. We aim to determine if maternal obesity alters major epigenetic modifications, DNA and RNA methylation, by affecting gene expression of methylation writers and erasers in the placenta. A cross-sectional study included maternal-fetal dyads presenting for scheduled cesarean delivery. Unlabored women at 37 weeks gestation or greater, with non-anomalous singleton pregnancy were enrolled if they had no maternal risk factors for placental diseases. Classified by prepregnancy BMI, two groups of women were eligible: 18.5 to 24.9 (non-obese) and greater than 30.0 (obese). Any medical complications of pregnancy, concern for fetal growth restriction or macrosomia, were exclusion criteria. Placental samples were obtained to measure DNA methylation, DNA methyltransferase Dnmt1/3a/3b and demethylase Tet1/2/3, RNA methylation, RNA methyltransferases and demethylases, and m6A RNA reader YTHDF1/3. Data were compared between obese and non-obese women. 12 obese (mean BMI 42.4 [IQR: 35.6-46.6]) and 12 non-obese patients (mean BMI 23.2 [IQR: 22.8-24.1]) have been enrolled. Placental DNA methylation levels were significantly higher in obese subjects. There was no difference of Dnmt1, 3a and 3b mRNA and protein expression between obese and non-obese subjects; however, the DNA demethylases Tet1, 2 and 3 were inhibited by obesity. Obesity reduced m6A levels but did not affect the expression of Mettl3 and Mettl14. Obesity suppressed the expression of key components of the Mettl3-Mettl14-WTAP complex including RBM15, WTAP and KIAA1429. Finally, maternal diabetes repressed the RNA reader YTHDF3, but did not affect the RNA demethylases FTO and ALKBH5. Our study demonstrates that DNA and RNA methylation plays an important role in the regulation of placental gene expression in non-complicated obese pregnancies by showing increased DNA methylation and decreased RNA methylation. These epigenetic findings may help explain the observed differences in perinatal outcomes between obese and non-obese pregnancies.

Obesity-induced changes in hepatocyte and skeletal myocyte expression of mRNAs encoding islet GPCR peptide ligands

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Transgenic mice expressing human IL-32 develop adipokine profiles resembling those of obesity-induced metabolic changes

Low-grade inflammation is associated with the development of insulin resistance in obese individuals. The present study aims to provide additional evidence strengthening the role of interleukin (IL)-32 in this key process. Using an IL-32 transgenic (IL-32tg) mouse model, we observed that IL-32tg fed a normal diet had greater body weight, due to greater accumulation of white adipose tissue (WAT) along with larger sized adipocytes. This led to metabolic consequences, with significant higher leptin levels and a trend towards hyperinsulinemia, indicating a phenotype resembling the metabolic syndrome. Adipocytes of IL-32tg mice were more prone to induce a pro-inflammatory response locally, which would be expected when predisposed to insulin resistance and type2 diabetes mellitus (T2D). In conclusion, our study provides novel evidence of a direct contribution of IL-32 to pathophysiological perturbations within the adipose tissue, possibly contributing to the metabolic syndrome that precedes frank insulin resistance and T2D. Future research should focus on the role of IL-32 in the obesity epidemic.

Anti-Obesity Effects of Lactobacillus fermentum CQPC05 Isolated from Sichuan Pickle in High-Fat Diet-Induced Obese Mice through PPAR-α Signaling Pathway.

Sichuan pickle is a traditional fermented food in China which is produced by the spontaneous fermentation of Chinese cabbage. In this study, the anti-obesity effects of a new lactic acid bacterium (Lactobacillus fermentum CQPC05, LF-CQPC05) isolated from Sichuan pickles were assessed in vivo. An obese animal model was established in mice by inducing obesity with high-fat diet. Both serum and tissues were collected from the mice, and then subjected to qPCR and Western blot analyses. The results showed that LF-CQPC05 could decrease the values of hepatosomatic, epididymal fat, and perirenal fat indices that were induced by a high-fat diet in mice. Moreover, LF-CQPC05 reduced the levels of alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C), and increased the level of high-density lipoprotein cholesterol (HDL-C) in both serum samples and liver tissues of obese mice fed with a high-fat diet. Pathological observations demonstrated that LF-CQPC05 could alleviate the obesity-induced pathological changes in the liver tissue of mice, and reduce the degree of adipocyte enlargement. The results of qPCR and Western blot analyses further indicated that LF-CQPC05 upregulated the mRNA and protein expression levels of lipoprotein lipase (LPL), PPAR-α: peroxisome proliferator-activated receptor-alpha (PPAR-α), (cholesterol 7 alpha-hydroxylase) CYP7A1, and carnitine palmitoyltransferase 1 (CPT1A), and downregulated the expression levels of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and CCAAT enhancer-binding protein alpha (C/EBP-α) in both liver tissue and epididymal adipose tissue. Taken altogether, this study reveals that LF-CQPC05 can effectively inhibit high-fat diet-induced obesity. Its anti-obesity effect is comparable to that of l-carnitine, and is superior to that of Lactobacillus delbrueckii subsp. bulgaricus, a common strain used in the dairy industry. Therefore, LF-CQPC05 is a high-quality microbial strain with probiotic potential.

Hepatocyte-specific HIF-1α ablation improves obesity-induced glucose intolerance by reducing first-pass GLP-1 degradation.

The decrease in incretin effects is an important etiologic component of type 2 diabetes with unknown mechanisms. In an attempt to understand obesity-induced changes in liver oxygen homeostasis, we found that liver HIF-1α expression was increased mainly by soluble factors released from obese adipocytes, leading to decreased incretin effects. Deletion of hepatocyte HIF-1α protected obesity-induced glucose intolerance without changes in body weight, liver steatosis, or insulin resistance. In-depth mouse metabolic phenotyping revealed that obesity increased first-pass degradation of an incretin hormone GLP-1 with increased liver DPP4 expression and decreased sinusoidal blood flow rate, reducing active GLP-1 levels in peripheral circulation. Hepatocyte HIF-1α KO blocked these changes induced by obesity. Deletion of hepatocyte HIF-2α did not change liver DPP4 expression but improved hepatic steatosis. Our results identify a previously unknown pathway for obesity-induced impaired beta cell glucose response (incretin effects) and the development of glucose intolerance through inter-organ communications.

Abstract 4951: Obesity-induced changes in baseline immune responses to pre-clinical breast cancer

Abstract Obesity is known to increase morbidity and mortality in breast cancer patients; however, the immunological contributions to such changes remain incompletely understood. Our long-term goal is to investigate the broad impact of obesity on anti-tumor immunity, with a particular focus on understanding the mechanisms underlying obesity-induced immune alterations and how these alterations may influence the use of immunotherapeutics in breast cancer patients. For our studies, we utilized a diet-induced model of obesity (DIO) in which mice were fed either a high-fat or low-fat diet to generate DIO or age-matched lean controls, respectively. Animals were then challenged with the syngeneic E0771 mammary carcinoma cell line. Tumor outgrowth was quantified by caliper measurements, bioluminescent imaging (BLI) via firefly luciferase-expressing E0771 (E0771-fLUC) cells, and endpoint tumor weights. Whole tumor immunogenetic gene expression profiles were evaluated using nanoString and immune populations were assessed via multi-parameter flow cytometry. All measures of tumor outgrowth reveal that obesity significantly increases primary tumor outgrowth and induces a variety of alterations to the immunogenetic profile. Additionally, obesity significantly alters the frequency of intra-tumoral immune populations, including decreases in CD4+ and CD8+ T cells, increases in granulocytic myeloid-derived suppressor cells (G-MDSCs) and myeloid dendritic cells (mDCs), and a trending decrease in total CD45+ tumor infiltrating leukocytes. These alterations are specific to the tumor environment, as they are not present in the spleens of tumor-bearing mice. Collectively these data implicate obesity as a causal agent in impairing anti-tumor immune responses to murine mammary tumors. Furthermore, they suggest several cellular candidates for future mechanistic investigations into obesity-induced alterations in breast cancer immunity. Citation Format: Justin Gibson, Prabhakara Nagareddy, Lyse Norian. Obesity-induced changes in baseline immune responses to pre-clinical breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4951.

Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability.

Obesity, defined as a state of positive energy balance with a body mass index exceeding 30 kg/m2 in adults and 95th percentile in children, is an increasing global concern. Approximately one-third of the world's population is overweight or obese, and in the United States alone, obesity affects one in six children. Meta-analysis studies suggest that obesity increases the likelihood of developing several types of cancer, and with poorer outcomes, especially in children. The contribution of obesity to cancer risk requires a better understanding of the association between obesity-induced metabolic changes and its impact on genomic instability, which is a major driving force of tumorigenesis. In this review, we discuss how molecular changes during adipose tissue dysregulation can result in oxidative stress and subsequent DNA damage. This represents one of the many critical steps connecting obesity and cancer since oxidative DNA lesions can result in cancer-associated genetic instability. In addition, the by-products of the oxidative degradation of lipids (e.g., malondialdehyde, 4-hydroxynonenal, and acrolein), and gut microbiota-mediated secondary bile acid metabolites (e.g., deoxycholic acid and lithocholic acid), can function as genotoxic agents and tumor promoters. We also discuss how obesity can impact DNA repair efficiency, potentially contributing to cancer initiation and progression. Finally, we outline obesity-related epigenetic changes and identify the gaps in knowledge to be addressed for the development of better therapeutic strategies for the prevention and treatment of obesity-related cancers.

Brain Innate Immune Response in Diet-Induced Obesity as a Paradigm for Metabolic Influence on Inflammatory Signaling.

Obesity is a predisposing factor for numerous morbidities, including those affecting the central nervous system. Hypothalamic inflammation is a hallmark of obesity and is believed to participate in the onset and progression of the obese phenotype, by promoting changes in neuronal functions involved in the control of metabolism. The activation of brain immune cells in the hypothalamus, which are represented by microglia and brain macrophages, is associated with obesity and has been the focus of intense research. Despite the significant body of knowledge gathered on this topic, obesity-induced metabolic changes in brain cells involved in innate immune responses are still poorly characterized due, at least in part, to limitations in the existing experimental methods. Since the metabolic state influences immune responses of microglia and other myeloid cells, the understanding and characterization of the effects of cellular metabolism on the functions of these cells, and their impact on brain integrity, are crucial for the development of efficient therapeutic interventions for individuals exposed to a long-term high fat diet (HFD). Here we review and speculate on the cellular basis that may underlie the observed changes in the reactivity and metabolism of the innate immune cells of the brain in diet-induced obesity (DIO), and discuss important points that deserve further investigation.

Obesity alters oestrogen metabolism and contributes to pulmonary arterial hypertension.

Obesity is a common comorbidity for pulmonary arterial hypertension (PAH). Additionally, oestrogen and its metabolites are risk factors for the development of PAH. Visceral adipose tissue (VAT) is a major site of oestrogen production; however, the influence of obesity-induced changes in oestrogen synthesis and metabolism on the development of PAH is unclear. To address this we investigated the effects of inhibiting oestrogen synthesis and metabolism on the development of pulmonary hypertension in male and female obese mice.We depleted endogenous oestrogen in leptin-deficient (ob/ob) mice with the oestrogen inhibitor anastrozole (ANA) and determined the effects on the development of pulmonary hypertension, plasma oestradiol and urinary 16α-hydroxyestrone (16αOHE1). Oestrogen metabolism through cytochrome P450 1B1 (CYP1B1) was inhibited with 2,2′,4,6′-tetramethoxystilbene (TMS).ob/ob mice spontaneously develop pulmonary hypertension, pulmonary vascular remodelling and increased reactive oxygen species production in the lung; these effects were attenuated by ANA. Oestradiol levels were decreased in obese male mice; however, VAT CYP1B1 and 16αOHE1 levels were increased. TMS also attenuated pulmonary hypertension in male ob/ob mice. Intra-thoracic fat from ob/ob mice and VAT conditioned media produce 16αOHE1 and can contribute to oxidative stress, effects that are attenuated by both ANA and TMS.Obesity can induce pulmonary hypertension and changes in oestrogen metabolism, resulting in increased production of 16αOHE1 from VAT that contributes to oxidative stress. Oestrogen inhibitors are now in clinical trials for PAH. This study has translational consequences as it suggests that oestrogen inhibitors may be especially beneficial in treating obese individuals with PAH.

Maternal High Fat Diet-Induced Obesity Modifies Histone Binding and Expression of Oxtr in Offspring Hippocampus in a Sex-Specific Manner.

Maternal obesity during pregnancy increases risk for neurodevelopmental disorders in offspring, although the underlying mechanisms remain unclear. Epigenetic deregulation associates with many neurodevelopmental disorders, and recent evidence indicates that maternal nutritional status can alter chromatin marks in the offspring brain. Thus, maternal obesity may disrupt epigenetic regulation of gene expression during offspring neurodevelopment. Using a C57BL/6 mouse model, we investigated whether maternal high fat diet (mHFD)-induced obesity alters the expression of genes previously implicated in the etiology of neurodevelopmental disorders within the Gestational Day 17.5 (GD 17.5) offspring hippocampus. We found significant two-fold upregulation of oxytocin receptor (Oxtr) mRNA in the hippocampus of male, but not female, GD 17.5 offspring from mHFD-induced obese dams (p < 0.05). To determine whether altered histone binding at the Oxtr gene promoter may underpin these transcriptional changes, we then performed chromatin immunoprecipitation (ChIP). Consistent with the Oxtr transcriptional changes, we observed increased binding of active histone mark H3K9Ac at the Oxtr transcriptional start site (TSS) in the hippocampus of mHFD male (p < 0.05), but not female, offspring. Together, these data indicate an increased vulnerability of male offspring to maternal obesity-induced changes in chromatin remodeling processes that regulate gene expression in the developing hippocampus, and contributes to our understanding of how early life nutrition affects the offspring brain epigenome.

Obesity and heart failure with preserved ejection fraction: a paradox or something else?

Obesity represents one of the most common comorbidities in patients with heart failure and preserved ejection fraction (HFpEF). Studies have shown that obesity is not only a comorbidity, but it could also be an important risk factor for HFpEF development. The mechanisms that connect obesity and HFpEF vary from obesity-induced hemodynamic changes to important biohumoral systems such as adipocitokines, renin-angiotensin-aldosterone and sympathetic nervous systems, natriuretic peptide, and oxidative stress. Studies agree about the negative influence of morbid obesity on cardiac remodeling and HFpEF development. However, there is still no agreement regarding the relationship between body mass index, as the most commonly used parameter of obesity, and HFpEF incidence or outcome in patients who already have HFpEF. The relationship varies from the linear to the U-shaped and, therefore, the "obesity paradox," which refers to the reduced risk in mildly overweight subjects in comparison with normal and underweight individuals, deserves more attention not only in the research but also in the clinical approach to these patients. In the absence of a satisfactory pharmacological approach, which would improve the outcome of this large group of patients, alternative methods such as weight loss and physical activity seem to provide encouraging results. This review article provides a clinical overview of the available data about the mechanisms that connect obesity and HFpEF, the most relevant studies on this topic, clinical relevance of the obesity paradox, and the therapeutic approach including weight loss and physical activity in obese patients with HFpEF.

Obesity-induced changes in T-cell metabolism are associated with impaired memory T-cell response to influenza and are not reversed with weight loss

Obesity-induced changes in T-cell metabolism are associated with impaired memory T-cell response to influenza and are not reversed with weight loss

Obesity-Induced Changes in T-Cell Metabolism Are Associated With Impaired Memory T-Cell Response to Influenza and Are Not Reversed With Weight Loss.

Obesity is an independent risk factor for increased influenza mortality and is associated with impaired memory T-cell response, resulting in increased risk of infection. In this study, we investigated if weight loss would restore memory T-cell response to influenza. Male C57BL/6J mice were fed either low-fat or high-fat diet to induce obesity. Once obesity was established, all mice received primary infection with influenza X-31. Following a recovery period, we switched half of the obese group to a low-fat diet to induce weight loss. Fifteen weeks after diet switch, all mice were given a secondary infection with influenza PR8, and memory T-cell function and T-cell metabolism were measured. Following secondary influenza infection, memory T-cell subsets in the lungs of obese mice were decreased compared to lean mice. At the same time, T cells from obese mice were found to have altered cellular metabolism, largely characterized by an increase in oxygen consumption. Neither impaired memory T-cell response nor altered T-cell metabolism was reversed with weight loss. Obesity-associated changes in T-cell metabolism are associated with impaired T-cell response to influenza, and are not reversed with weight loss.