Obesity, Inflammation, and Insulin Resistance

Harvard University, Cambridge, Massachusetts, United States
Gastroenterology (Impact Factor: 16.72). 06/2007; 132(6):2169-80. DOI: 10.1053/j.gastro.2007.03.059
Source: PubMed


Weight gain and obesity are major risk factors for conditions and diseases ranging from insulin resistance and type 2 diabetes mellitus to atherosclerosis and the sequelae of nonalcoholic fatty liver disease. A chronic, subacute state of inflammation often accompanies the accumulation of excess lipid in adipose tissue and liver (hepatic steatosis), evidenced by changes in both inflammatory cells and biochemical markers of inflammation. These changes can be seen in the involved tissues and systemically, in terms of elevated circulating levels of inflammatory markers. The link between obesity and inflammation has therefore raised the important question of whether obesity-induced inflammation plays a pathogenic role in the development and progression of these disorders. We review the rapidly expanding body of animal and clinical data that support potential roles for inflammation in the pathogenesis of insulin resistance and type 2 diabetes mellitus.

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Available from: Laura Herrero, Jan 23, 2015
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    • "e l s e v i e r . c o m / c y t o k i n e for gallstones, such as obesity, serum lipids, and diabetes have also been linked to inflammation [3] [4] [5]. Furthermore, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with a reduction in gallbladder cancer [6], again suggesting that inflammation is an important mechanism in gallbladder pathogenesis. "
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    ABSTRACT: Gallbladder disease is highly related to inflammation, but the inflammatory processes are not well understood. Bile provides a direct substrate in assessing the local inflammatory response that develops in the gallbladder. To assess the reproducibility of measuring inflammatory markers in bile, we designed a methods study of 69 multiplexed immune-related markers measured in bile obtained from gallstone patients. To evaluate assay performance, a total of 18 bile samples were tested twice within the same plate for each analyte, and the 18 bile samples were tested on two different days for each analyte. We used the following performance parameters: detectability, coefficient of variation (CV), intraclass correlation coefficient (ICC), and percent agreement (concordance among replicate measures above and below detection limit). Furthermore, we examined the association of analyte levels with gallstone characteristics such as type, numbers, and size. All but 3 analytes (Stem Cell Factor, SCF; Thrombopoietin, TPO; sIL-1RI) were detectable in bile. 52 of 69 (75.4%) analytes had detectable levels for at least 50% of the subjects tested. The within-plate CVs were ⩽25% for 53 of 66 (80.3%) detectable analytes, and across-plate CVs were ⩽25% for 32 of 66 (48.5%) detectable analytes. Moreover, 64 of 66 (97.0%) analytes had ICC values of at least 0.8. Lastly, the percent agreement was high between replicates for all of the analytes (median; within plate, 97.2%; across plate, 97.2%). In exploratory analyses, we assessed analyte levels by gallstone characteristics and found that levels for several analytes decreased with increasing size of the largest gallstone per patient. Our data suggest that multiplex assays can be used to reliably measure cytokines and chemokines in bile. In addition, gallstone size was inversely related to the levels of select analytes, which may aid in identifying critical pathways and mechanisms associated with the pathogenesis of gallbladder diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Cytokine 03/2015; 73(1):84-90. DOI:10.1016/j.cyto.2015.01.033 · 2.66 Impact Factor
    • "People with obesity have been reported to have higher production of inflammatory cytokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β[1]. Additionally , many obesity-related diseases such as cardiovascular disease and type 2 diabetes mellitus seem to be associated with inflammation [1] [2] [3]. Obesity is reported to contribute to the impairment of human T-cell function, which in turn is associated with a higher incidence of infection in obese people [4]. "
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    ABSTRACT: Obesity has been reported to impair immune functions and lead to low-grade long-term inflammation; however, studies that have investigated the impact of weight loss on these among the young and slightly obese are limited. Thus, we investigated the effect of a 12-week weight management program with behavioral modifications on cell-mediated immune functions and inflammatory responses in young obese participants. Our hypothesis was that weight loss would result in improved immune functions and decreased inflammatory responses. Sixty-four participants (45 obese and 19 normal weight) finished the program. Obese (body mass index ≥25) participants took part in 5 group education and 6 individual counseling sessions. Normal-weight (body mass index 18.5-23) participants only attended 6 individual sessions. The goal for the obese was to lose 0.5 kg/wk by reducing their intake by 300 to 500 kcal/d and increasing their physical activity. Program participation resulted in a modest but significant decrease in weight (2.7 ± 0.4 kg, P < .001) and lipopolysaccharide-stimulated interleukin-1β production (from 0.85 ± 0.07 to 0.67 ± 0.07 ng/mL, P < .05) in the obese. In the obese group, increase in phytohemagglutinin-stimulated interleukin-10 production, a TH2 and anti-inflammatory cytokine, approached significance after program participation (from 6181 ± 475 to 6970 ± 632 pg/mL, P = .06). No significant changes in proliferative responses to the optimal concentration of concanavalin A or phytohemagglutinin were observed in the obese after program participation. Collectively, modest weight loss did not change the cell-mediated immune functions significantly but did attenuate the inflammatory response in young and otherwise healthy obese adults. Copyright © 2015. Published by Elsevier Inc.
    Nutrition Research 02/2015; 35(4). DOI:10.1016/j.nutres.2015.02.004 · 2.47 Impact Factor
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    • "Genetic deletion of Fas protects against adipose tissue inflammation, insulin resistance and hepatic steatosis in mice fed a high fat diet[37]. TNF-α has also been implicated in obesity-associated metabolic syndrome[28]. However, the role of TRAIL and its cognate death receptors in lipotoxicity has not been explored. "
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    ABSTRACT: Low-grade chronic inflammation is a cardinal feature of the metabolic syndrome, yet its pathogenesis is not well defined. The purpose of this study was to examine the role of TRAIL receptor (TR) signaling in the pathogenesis of obesity-associated inflammation utilizing mice with the genetic deletion of TR. TR knockout (TR(-/-)) mice and their littermate wild-type (WT) mice were fed a diet high in saturated fat, cholesterol and fructose (FFC) or chow. Metabolic phenotyping, liver injury, and liver and adipose tissue inflammation were assessed. Chemotaxis and activation of mouse bone marrow-derived macrophages (BMDMϕ) was measured. Genetic deletion of TR completely repressed weight gain, adiposity and insulin resistance in FFC-fed mice. Moreover, TR(-/-) mice suppressed steatohepatitis, with essentially normal serum ALT, hepatocyte apoptosis and liver triglyceride accumulation. Gene array data implicated inhibition of macrophage-associated hepatic inflammation in the absence of the TR. In keeping with this, there was diminished accumulation and activation of inflammatory macrophages in liver and adipose tissue. TR(-/-) BMDMφ manifest reduced chemotaxis and diminished activation of nuclear factor-κ B signaling upon activation by palmitate and lipopolysaccharide. These data advance the concept that macrophage-associated hepatic and adipose tissue inflammation of nutrient excess requires TR signaling. Copyright © 2014. Published by Elsevier B.V.
    Journal of Hepatology 11/2014; 62(5). DOI:10.1016/j.jhep.2014.11.033 · 11.34 Impact Factor
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