Role of adipokines in complications related to obesity. A review

Gnacińska, Maria; Małgorzewicz, Sylwia; Stojek, Magdalena; Łysiak−Szydłowska, Wiesława; Sworczak, Krzysztof

doi:10.2478/v10039-009-0035-2

Cited by 145 publications

(126 citation statements)

References 55 publications

(41 reference statements)

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“…This TRE is also conserved in the rat (20). We therefore further evaluated whether the expression of the C/ebpα mRNA was affected by NCOR1ΔID in the epididymal fat pad of Thra1 PV/+ Ncor1 ΔID/ΔID mice.…”

Section: Expression Of Ncor1δid Lessens the Extent Of Retarded Growth Inmentioning

confidence: 99%

Nuclear receptor corepressor (NCOR1) regulates in vivo actions of a mutated thyroid hormone receptor α

Fozzatti

Kim

Park

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Genetic evidence from patients with mutations of the thyroid hormone receptor α gene (THRA) indicates that the dominant negative activity of mutants underlies the pathological manifestations. However, the molecular mechanisms by which TRα1 mutants exert dominant negative activity in vivo are not clear. We tested the hypothesis that the severe hypothyroidism in patients with THRA mutations is due to an inability of TRα1 mutants to properly release the nuclear corepressors (NCORs), thereby inhibiting thyroid hormone-mediated transcription activity. We crossed Thra1 PV mice, expressing a dominant negative TRα1 mutant (TRα1PV), with mice expressing a mutant Ncor1 allele (Ncor1 ΔID mice) that cannot recruit the TR or PV mutant. TRα1PV shares the same C-terminal mutated sequences as those of patients with frameshift mutations of the THRA gene. Remarkably, NCOR1ΔID ameliorated abnormalities in the thyroid-pituitary axis of Thra1 PV/+ mice. The severe retarded growth, infertility, and delayed bone development were partially reverted in Thra1 PV/+ mice expressing NCOR1ΔID. The impaired adipogenesis was partially corrected by de-repression of peroxisome-proliferator activated receptor γ and CCAAT/enhancerbinding protein α gene, due to the inability of TRα1PV to recruit NCOR1ΔID to form a repressor complex. Thus, the aberrant recruitment of NCOR1 by TRα1 mutants could lead to clinical hypothyroidism in humans. Therefore, therapies aimed at the TRα1-NCOR1 interaction or its downstream actions could be tested as potential targets in treating TRα1 mutant-mediated hypothyroidism in patients.growth retardation | lipid metabolism | fertility defect T he thyroid hormone T3 regulates growth and development and maintains metabolic homeostasis in humans. The genomic signaling by T3 is via the thyroid hormone receptor (TR) isoforms α1, β1, and β2, which are encoded by the THRA and THRB genes located on two different chromosomes. These TR isoforms share extensive sequence homology in the DNA and T3 binding domains but differ in the amino terminal A/B domains (1). TR binds to the thyroid hormone response elements (TREs) and recruits nuclear coregulatory proteins to regulate gene transcription. In the absence of T3, TRs recruit the nuclear corepressors (NCOR1 and NCOR2) for transcriptional repression on the T3 positively regulated genes. In the presence of T3, the T3-bound TR undergoes structural changes, resulting in the release of corepressors, allowing recruitment of nuclear receptor coactivators (e.g., SRC-1) to facilitate transcription activation (2, 3).The critical roles of TR in mediating biological functions of T3 are clearly evident, in that mutations of the THRB gene cause resistance to thyroid hormone (RTH) (3). The intriguing observation that no mutations of the THRA gene were ever found in RTH patients raised the possibilities that mutations of the THRA gene could be embryonic lethal or could confer different clinical manifestations. These possibilities were explored by using a powerful mouse genetic approach. Targeting a ...

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Section: Expression Of Ncor1δid Lessens the Extent Of Retarded Growth Inmentioning

confidence: 99%

Nuclear receptor corepressor (NCOR1) regulates in vivo actions of a mutated thyroid hormone receptor α

Fozzatti

Kim

Park

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…In particular, the main cytokines associated with inflammation and secreted by adipocytes are interleukins (i.e. IL-6), monocyte chemotactic protein I (MCP-I), leptin and resistin (2 ). Corrado et al (3) underlined the importance of assessing acute-phase proteins (high sensitive C Reactive Protein, hsCRP, and fibrinogen), which are independently associated with the incidence of coronary events.…”

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confidence: 99%

Oxidative Stress and Low-Grade Inflammatory Status as Cardiometabolic Risk Factors in Italian Occupational Overweight/Obese Subjects

et al. 2013

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Obesity is associated with increased risk of cardiometabolic diseases. Adipocytokines (e.g. leptin), produced by the endocrine function of adipose tissue, can contribute to cardiometabolic risk in overweight and obese people. Oxidative stress, imbalance between oxidants and antioxidants, is considered a cardiovascular risk factor. High serum oxidized LDL (oxLDL) levels, marker of lipid peroxidation, a primary cause of atherosclerosis, can contribute to its progression. The aims of this study are to assess markers of oxidative status and cytokine profile and evaluate their role as cardiometabolic risk factors and possible correlations. In this cross-sectional study, we enrolled 76 occupational overweight-obese adults (46 females, 30 males; aged 46.8±9.5; BMI 33.7±4.8 kg/m') without any previous cardiovascular disease. Oxidative status was measured by evaluating serum Reactive Oxygen Species (ROS) levels, Total Antioxidant Capacity (TAC) and oxLDL concentrations. All subjects' soluble cytokine and adhesion molecule levels were evaluated by cytofluorimetric method and compared with 35 controls matched for sex and age. ROS and oxLDL levels were high in 84% and 92% of the study population, respectively, despite adequate TAC (68%). Female ROS levels were significantly higher than those of males (414±99.3 vs 318±48.2 UCarr, p

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“…Indeed, CB1R inhibition may act to diminish aging‐associated lipogenesis, a process known to be transduced in response to CB1R activation, as well as promoting increased lipolytic drive either directly or indirectly, for example through activation of the sympathoadrenal system (Jbilo et al ., 2005; Molhoj et al ., 2010). Furthermore, the anti‐inflammatory response conveyed by the CB1R blocker in aged epididymal fat may also contribute to its insulin‐sensitizing actions, in particular considering the fact that adipose tissue serves as a key site for the production and secretion of insulin‐desensitizing inflammatory cytokines such as IL‐6 and TNFα (Gnacinska et al ., 2009; Gustafson, 2010). …”

Section: Discussionmentioning

confidence: 99%

CB1 receptor blockade counters age‐induced insulin resistance and metabolic dysfunction

et al. 2016

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SummaryThe endocannabinoid system can modulate energy homeostasis by regulating feeding behaviour as well as peripheral energy storage and utilization. Importantly, many of its metabolic actions are mediated through the cannabinoid type 1 receptor (CB1R), whose hyperactivation is associated with obesity and impaired metabolic function. Herein, we explored the effects of administering rimonabant, a selective CB1R inverse agonist, upon key metabolic parameters in young (4 month old) and aged (17 month old) adult male C57BL/6 mice. Daily treatment with rimonabant for 14 days transiently reduced food intake in young and aged mice; however, the anorectic response was more profound in aged animals, coinciding with a substantive loss in body fat mass. Notably, reduced insulin sensitivity in aged skeletal muscle and liver concurred with increased CB1R mRNA abundance. Strikingly, rimonabant was shown to improve glucose tolerance and enhance skeletal muscle and liver insulin sensitivity in aged, but not young, adult mice. Moreover, rimonabant‐mediated insulin sensitization in aged adipose tissue coincided with amelioration of low‐grade inflammation and repressed lipogenic gene expression. Collectively, our findings indicate a key role for CB1R in aging‐related insulin resistance and metabolic dysfunction and highlight CB1R blockade as a potential strategy for combating metabolic disorders associated with aging.

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Role of adipokines in complications related to obesity. A review

Cited by 145 publications

References 55 publications

Nuclear receptor corepressor (NCOR1) regulates in vivo actions of a mutated thyroid hormone receptor α

Nuclear receptor corepressor (NCOR1) regulates in vivo actions of a mutated thyroid hormone receptor α

Oxidative Stress and Low-Grade Inflammatory Status as Cardiometabolic Risk Factors in Italian Occupational Overweight/Obese Subjects

CB1 receptor blockade counters age‐induced insulin resistance and metabolic dysfunction

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