Effects of the Obese (ob/ob) Genotype on Spleen Cell Immune Function

Abstract

Spleen cells from mice homozygous for the obese (ob) mutation killed DBA/2 mastocytoma target cells less well than spleen cells from lean littermates or unrelated age- and sex-matched controls of the same strain. Killing was impaired only when the attacker cells were primed in vivo, not following in vitro priming. Hence the effect of the ob/ob genotype is not to produce an irreversible functional change in the lymphocyte, but rather to produce an environment in which lymphocytes are less able to react to priming antigen. Not only were the spleen cells of in vivo primed obese mice less active than those of lean controls, but also their number per spleen was significantly decreased. Such a quantitative difference was no longer found in adrenalectomised animals, but the qualitative difference in spleen cell cytotoxic activity still occurred. This suggests that adrenocortical hyperfunction may affect immune function in obese mice, without necessarily being the only factor in the in vivo environment of obese mouse spleen cells capable of depressing cellular immune reactivity.

Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: Role of tumor necrosis factor α and IL-18

“…mice, suggesting that supraphysiologic amounts of leptin may influence lymphocyte cellularity in the thymus. In addition, as previously demonstrated (15)(16)(17)(18)(19), spleen weight was significantly reduced in ob͞ob mice compared with ϩ͞? mice, and leptin-replacement normalized spleen weight (spleen weight was 40.00 Ϯ 8.52, 65.00 Ϯ 2.89, and 63.70 Ϯ 3.75 mg in ob͞ob, leptin-replaced ob͞ob, and ϩ͞?…”

“…Although several studies report the presence of lymphoid atrophy in ob͞ob mice (15)(16)(17)(18)(19), to our knowledge the present data are the first showing reduced T cell-mediated inflammatory responses in vivo in ob͞ob mice. The observation that ob͞ob mice are protected from liver damage induced by T cell-activating stimuli such as Con A or PEA is in striking contrast to data demonstrating increased sensitivity of ob͞ob mice to proinflammatory monocyte͞macrophage-activating stimuli, particularly LPS and TNF-␣ (9-11).…”

“…Hyperresponsiveness to monocyte͞macrophage-activating stimuli, i.e., endotoxin [lipopolysaccharide (LPS)] or tumor necrosis factor (TNF) ␣, is present in leptin-deficient (ob͞ob) mice (9)(10)(11). Additionally, decreased circulating leptin levels are associated with reduced lymphocyte cellularity in the thymus and spleen (15)(16)(17)(18)(19).…”

Rodent models of diabetic cardiomyopathy

“…However, it is unclear whether peripheral organs, including the heart, are indeed resistant to the action of leptin, and the potential contribution of impaired cardiac leptin action to abnormal cardiac function in ob/ob mice remains to be elucidated. Leptin signaling has significant effects on immune cells, and defects in innate and adaptive immunity have been described in ob/ob mice (Sheena and Meade, 1978;Meade et al, 1979;La Cava and Matarese, 2004;Matarese et al, 2005;Otero et al, 2006). For example, cardiac injury induced by viral myocarditis is more pronounced in ob/ob mice than in their lean controls, probably owing to a defective T-cell response (Kanda et al, 2004).…”

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

“…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).…”