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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    • "control by diet alone is difficult, requiring therapy with drugs, but the adverse side effects associated with available drugs have become a limiting factor, demanding the discovery of novel molecules targeting various pathways involved in the pathogenesis of obesity (Bray, 2013). Adipose tissue is heterogeneous mix of adipocytes, preadipocytes, immune cells, and endothelium, and it responds rapidly and dynamically to alterations in nutrient excess through adipocyte hypertrophy and hyperplasia.In addition to functioning as the principal energy storage depot, adipose tissue secretes hormones that contribute to energy homeostasis(Friedman and Halaas 1998;Shoelson, Herrero et al., 2007).Thus, understanding the molecular mechanisms of adipocyte differentiation is necessaryfor designing effective drug therapies for the treatment of obesity. Several studies screening for antiobesity materials have focused to study the effect of drugs on the processes of adipocyte proliferation and differentiation(Lin, Della-Fera et al., 2005; Kim, Della- Fera et al., 2006;Yang, Della-Fera et al., 2006). "
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    ABSTRACT: Combinational therapies are among the attractive treatment strategies for the pathological states where multiple regulatory mechanisms contribute to the development and the progression of the disease. In our present study, we investigated the effects of combination of Suberoylanilide hydroxamic acid [SAHA] and O2', O3', O5'-tri-acetyl-N6-(3-hydroxylaniline) adenosine [THA] on viability, adipogenesis and apoptosis in 3T3-L1 pre-adipocytic cell line. Mature adipocytes when treated individually with either SAHA or THA decreased cell viability but the combination of SAHA and THA caused an enhanced decrease in cell viability. The combination of drugs also showed an enhanced inhibition of adipocyte differentiation as monitored by Oil Red O Staining. The western blot analysis revealed that SAHA and THA when used in combination decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPAR-γ) and CCAAT/enhancer binding protein (C/EBPα), both of which act as key regulators of adipogenesis. Furthermore, the combination of drugs increased the expression levels of Bcl-2 associated X protein (Bax) which is a pro-apoptotic protein involved in mediating apoptosis. Thus, the combination of SAHA and THA se
    International Journal of Biological & Pharmaceutical Research 10/2015; 6(10):831-8.
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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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