Cell-mediated immunity in genetically obese (C57BL/6J ob/ob) mice

Chandra, R. K.

doi:10.1093/ajcn/33.1.13

Cited by 164 publications

(100 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, human white blood cell counts are correlated with body mass index and serum leptin levels [23]. Moreover, diminished cell-mediated immunity and decreased lymphocyte counts have been reported in ob/ob and db/db mice [24,25].We demonstrate here that leptin receptor messenger RNA is expressed in lymphoid tissue, and that leptin both restores the decrease in lymphocyte numbers normally observed in fasted mice and prevents apoptosis of lymphocytes in steroidinjected mice. Consistent with the observed anti-apoptotic effect of leptin, we observed up-regulation of the bcl-xL gene by leptin.…”

supporting

confidence: 56%

Leptin inhibits stress-induced apoptosis of T lymphocytes

Fujita¹,

Murakami²,

Ogawa³

et al. 2002

Clinical and Experimental Immunology

145

106

View full text Add to dashboard Cite

Nutritional status and immune function are closely related [1][2][3]. Food deprivation leads to impaired immune responses and an increase in the incidence of infectious disease, although the mechanism by which this occurs has yet to be elucidated. Adipose tissue preserves energy homeostasis through the storage of triglycerides. However, it has been found recently that a number of cytokine-like molecules, such as leptin [4], tumour necrosis factor-a (TNF-a) [5] and plasminogen activator inhibitor-1 (PAI-1) [6] are secreted from adipocytes, suggesting that adipose tissue may also play a role in the regulation of the immune and haematopoietic systems.Leptin is secreted specifically by adipocytes [4], and serum leptin levels are proportional to body mass index. However, the placenta [7] and stomach [8] provide additional sources of leptin. Leptin decreases food intake, increases energy expenditure and reduces body weight via leptin receptors within the ventromedial hypothalamus [9], where leptin functions to inhibit the production of neuropeptide Y which stimulates food intake [10]. The murine leptin and leptin-receptor mutants ob/ob and db/db, respectively, serve as animal models of obesity, and develop marked obesity and diabetes due to deficiencies in leptin signalling [11]. In contrast, leptin transgenic mice with elevated plasma leptin concentrations lack brown or white adipose tissue, show reduced food intake, and are markedly lean in comparison with non-transgenic littermates [12].The leptin receptor is expressed in peripheral tissues such as the kidney, lung and adrenal gland [13,14], and several in vitro studies have demonstrated that leptin acts directly on the leptin receptor [15,16]. There are at least five splice variants of the leptin receptor Ob-Ra-Ob-Re, and one of these five variants, Ob-Rb, possesses a long intracellular domain demonstrating homology with gp130, a subunit of the IL-6 family of cytokine receptors [17]. On the other hand, Ob-Ra, one of the shortest forms of the leptin receptor, lacks the STAT3 activation domain and is not considered essential for signal transduction [18].Recent studies have revealed that Ob-Rb is expressed in fetal liver haematopoietic precursor cells, bone marrow and peripheral T cells [14,19]. In adult human bone marrow, both CD34 positive and negative cells express leptin receptor. These findings suggest the possibility that leptin not only regulates body weight, but also modulates the immune system. Indeed, leptin increases the proliferation of haematopoietic stem cell populations at the multilineage progenitor level [18], enhances alloproliferative mixed-lymphocyte reactions, and reverses cellular immune function in fasted mice [20]. In addition, leptin might act as a growth factor for both myeloid leukaemic cells [21] and lung cancer cells [22]. In addition, human white blood cell counts are correlated with body mass index and serum leptin levels [23]. Moreover, diminished cell-mediated immunity and decreased lymphocyte counts have been reported in ob/ob and db...

show abstract

supporting

confidence: 56%

Leptin inhibits stress-induced apoptosis of T lymphocytes

Fujita¹,

Murakami²,

Ogawa³

et al. 2002

Clinical and Experimental Immunology

145

106

View full text Add to dashboard Cite

show abstract

“…Leptin-deficient rodents used as models for insulin resistance are hyperinsulinemic, insulin-resistant, and immuno-compromised (Meade et al 1979, Chandra 1980, Zhang et al 1994, Lord et al 1998, Howard et al 1999. Importantly, these observations are, in part, opposite to the human scenario where obese individuals that develop insulin resistance exhibit high leptin levels and an induction of inflammation (Gregor & Hotamisligil 2011).…”

Section: Discussionmentioning

confidence: 99%

Hyperinsulinemia induces insulin resistance and immune suppression via Ptpn6/Shp1 in zebrafish

Marín-Juez¹,

Jong-Raadsen²,

Yang³

et al. 2014

Journal of Endocrinology

View full text Add to dashboard Cite

Type 2 diabetes, obesity, and metabolic syndrome are pathologies where insulin resistance plays a central role, and that affect a large population worldwide. These pathologies are usually associated with a dysregulation of insulin secretion leading to a chronic exposure of the tissues to high insulin levels (i.e. hyperinsulinemia), which diminishes the concentration of key downstream elements, causing insulin resistance. The complexity of the study of insulin resistance arises from the heterogeneity of the metabolic states where it is observed. To contribute to the understanding of the mechanisms triggering insulin resistance, we have developed a zebrafish model to study insulin metabolism and its associated disorders. Zebrafish larvae appeared to be sensitive to human recombinant insulin, becoming insulin-resistant when exposed to a high dose of the hormone. Moreover RNA-seq-based transcriptomic profiling of these larvae revealed a strong downregulation of a number of immune-relevant genes as a consequence of the exposure to hyperinsulinemia. Interestingly, as an exception, the negative immune modulator protein tyrosine phosphatase nonreceptor type 6 (ptpn6) appeared to be upregulated in insulin-resistant larvae. Knockdown of ptpn6 was found to counteract the observed downregulation of the immune system and insulin signaling pathway caused by hyperinsulinemia. These results indicate that ptpn6 is a mediator of the metabolic switch between insulin-sensitive and insulin-resistant states. Our zebrafish model for hyperinsulinemia has therefore demonstrated its suitability for discovery of novel regulators of insulin resistance. In addition, our data will be very useful in further studies of the function of immunological determinants in a non-obese model system.

show abstract

“…Plasma levels of leptin have also been investigated in patients with Rett syndrome (n=16), where it was found that leptin was significantly increased compared to healthy controls (n=16), but also did not correlate with obesity (Blardi et al, 2008), suggesting that there may be more to the actions of leptin in neurodevelopment than weight balance. The immunomodulatory properties of leptin were first reported on a mouse model, in which obese mice were found to have impaired cell-mediated and humoral immunity, attributed to possible lack of leptin (Chandra, 1980). The epigenetic status in adulthood was shown to be directionally dependent on prenatal nutritional status (Gluckman et al, 2007) and neonatal leptin administration late in the phase of developmental plasticity was able to reverse the developmental programming in rats (Vickers et al, 2005).…”

Section: Other Perinatal Risk Factorsmentioning

confidence: 99%