Systemic immunity of obese-diabetes model (db/db) mice

Abstract

Obesity has recently been defined as a chronic inflammatory disease and is considered as a major cause of adult health problems including incurable diseases like diabetes and cancer. In this study, the systemic immunity, including the innate and adaptive immunity parameters, of naturally occurring (leptin receptor mutation) obesity-diabetes mice (db/db) was examined to increase our knowledge of these mice for obesity-related studies. Severe fatty liver with blood engorgement was observed in the db/db mice. Compared to background C57BL/6J mice, the adaptive immunity, as measured by mitogen-induced T and B cell proliferation and cytokine release, was significantly suppressed in db/db mice. However, significant upregulation of innate immune-inflammatory parameters including macrophage function and NK cell activity was observed in db/db mice without external stimulation. These data conclusively confirm the systemic immune-inflammatory micro-environment with suppressed adaptive immunity of db/db mice, which may cause the secondary obesity-related life-threatening diseases like diabetes or cancer.Keywords Obese-diabetes model, Systemic immunity, db/db mice In modern society, obesity is considered a disease that causes incurable adult health problems including type II diabetes, cardiovascular disorders and cancer 1-5 . Recent findings indicate that obesity is a chronic inflammatory disease 3,6,7 . Increased NF-κB nuclear binding is known to be related with inflammation in obesity 3 . Inflammation-related molecules like adiponectin, cytokines (TNF-α, IL-1β or IL-6) and chemokines are secreted from white adipocytes and macrophages. The infiltration of macrophages into the adipose tissue observed in the obese state worsens the inflammatory situation of white fat 3 . Plasma-circulating adipokines and pro-inflammatory cytokines that are secreted from the cells with monocyte/macrophage phenotype may represent a mechanism for several obese-related adult health problems like type II diabetes [3][4][5]9 . Along with a clear association between immune-inflammatory responses and obesity, systemic cellular immune modulatory responses other than inflammation in obese targets have been also reported. Obesity-related systemic immune responses such as cytokine dysregulation and lipotoxicity can cause insulin resistance and metabolic disease, which increase the lethality in patients through internal organ destruction or infection 9,10 . Evidences from human as well as animal model suggest that obesity may be associated with immunodeficiency state including significantly impaired T cell responses 5-8 . Interestingly, modulation of regulatory T cell responses confirmed by increased transcription factor FoxP 3 in the lymphocytes was observed in leptin-deficient obese (ob/ob) mice 2 . In this study, the systemic immunity, including the innate and adaptive immune parameters, of naturally occurring obese-diabetic mice (db/db; leptin receptor mutation) was examined to increase our basic knowledge for obesity-related studies. Leptin is adipocyt...

Leptin antagonism inhibits prostate cancer xenograft growth and progression

“…Interpretation of this finding is limited and warrants further investigation in an intact immune system. Though this is consistent with reports of altered immune response in transgenic non-immunocompromised animals lacking LEPR (db/db), where db/db mice exhibited increased innate immune-inflammatory factors, like macrophage function and NK cell activity, without external stimulation (Lee et al, 2010) and in those modelling atherosclerosis exhibited a regulatory T-cell immune response, protecting mice from atherosclerotic lesions (Taleb et al, 2007).…”

Anti-obesity Effect of Alkaline Reduced Water in High Fat-Fed Obese Mice

“…[3][4][5] Excessive intake of dietary fats influences the progression of obesity, 6) which is characterized by accumulation of body fats marked by abnormal increase in adipose tissue mass and liver fats (adiposity), dysregulated levels of adipokines, and imbalance between pro-and anti-inflammatory cytokine. [7][8][9] The complexity of these pathogenetic mechanisms of obesity poses a challenge to the development of effective therapy. In that context, there has been growing concern for the need of newer therapeutic strategies that directly deal with these mechanisms.…”

Chronic stress aggravates glucose intolerance in leptin receptor-deficient (db/db) mice

“…Adipose tissue in obese and diabetic individuals might develop an inflammatory milieu which ultimately leads to insulin resistance (Patel et al 2013). Macrophages, immune-inflammatory cells and natural killer cells in innate immunity are significantly activated in leptin receptordeficient mice (Lee et al 2010). The present data could support the link between a dysregulated immune and metabolic function since leptin is also known to modulate lymphocyte proliferation, apoptosis and cytokine secretion (Fantuzzi and Faggioni 2000;Farooqi et al 2002).…”