Leptin, a neuroendocrine mediator of immune responses, inflammation, and sickness behaviors

Carlton, Elizabeth D.; Demas, Gregory E.; French, Susannah S.

doi:10.1016/j.yhbeh.2012.04.010

Cited by 74 publications

(63 citation statements)

References 143 publications

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“…6) (28). As the literature shows, IGF-I has strong adipogenic and anti-inflammatory properties (21,24,30,32,66,70,75,80), as does adiponectin (14,47,63,68), whereas leptin is known to be proinflammatory and adipolytic (7,14,47). IL-6, another cytokine known to have proinflammmatory and adipolytic properties (34,40,42), was also consistently decreased following BAT transplants.…”

Section: Discussionmentioning

confidence: 94%

Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

Gunawardana

Piston

2015

American Journal of Physiology-Endocrinology and Metabolism

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Gunawardana SC, Piston DW. Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant. Am J Physiol Endocrinol Metab 308: E1043-E1055, 2015. First published April 21, 2015; doi:10.1152/ajpendo.00570.2014.-Traditional therapies for type 1 diabetes (T1D) involve insulin replacement or islet/pancreas transplantation and have numerous limitations. Our previous work demonstrated the ability of embryonic brown adipose tissue (BAT) transplants to establish normoglycemia without insulin in chemically induced models of insulin-deficient diabetes. The current study sought to extend the technique to an autoimmune-mediated T1D model and document the underlying mechanisms. In nonobese diabetic (NOD) mice, BAT transplants result in complete reversal of T1D associated with rapid and longlasting euglycemia. In addition, BAT transplants placed prior to the onset of diabetes on NOD mice can prevent or significantly delay the onset of diabetes. As with streptozotocin (STZ)-diabetic models, euglycemia is independent of insulin and strongly correlates with decrease of inflammation and increase of adipokines. Plasma insulinlike growth factor-I (IGF-I) is the first hormone to increase following BAT transplants. Adipose tissue of transplant recipients consistently express IGF-I compared with little or no expression in controls, and plasma IGF-I levels show a direct negative correlation with glucose, glucagon, and inflammatory cytokines. Adipogenic and anti-inflammatory properties of IGF-I may stimulate regeneration of new healthy white adipose tissue, which in turn secretes hypoglycemic adipokines that substitute for insulin. IGF-I can also directly decrease blood glucose through activating insulin receptor. These data demonstrate the potential for insulin-independent reversal of autoimmune-induced T1D with BAT transplants and implicate IGF-I as a likely mediator in the resulting equilibrium. type 1 diabetes; brown adipose tissue; insulin independent; transplantation; insulin-like growth factor I TYPE 1 DIABETES (T1D) is characterized by autoimmune-mediated destruction of pancreatic ␤-cells, resulting in absolute deficiency of insulin and loss of glycemic control. Treatments for T1D, despite having been refined over many years, are geared mainly toward replacing insulin, which involves numerous risks and limitations. Direct insulin replacement via daily injections or insulin pump does not cure the disease and requires life-long repeated administration. In addition to the inconvenience, direct insulin therapy requires careful monitoring of dosage and blood glucose levels and can lead to potentially fatal hypoglycemic episodes. Pancreas transplantation, the only available treatment with a good chance of long-term insulin independence, requires invasive surgery and life-long immunosuppressive therapy. Islet transplantation, although less invasive, is limited by the availability of donor tissue and the need for immunosuppression, and patients often return to insulin dependence in the long...

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Section: Discussionmentioning

confidence: 94%

Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

Gunawardana

Piston

2015

American Journal of Physiology-Endocrinology and Metabolism

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“…Additional candidates that deserve further study and are not directly involved with the stress response are growth hormone, leptin and ghrelin. These metabolic hormones regulate the immune system (Hattori, 2009;Baatar et al, 2011;Carlton et al, 2012) but are also altered by experimental sleep loss (Mullington et al, 2009). …”

Section: Sleep Deprivation Suppresses Peripheral and Hypothalamic Il-mentioning

confidence: 99%

Sleep deprivation attenuates endotoxin-induced cytokine gene expression independent of day length and circulating cortisol in male Siberian hamsters (Phodopus sungorus)

Ashley

Walton

Haim

et al. 2013

Journal of Experimental Biology

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SUMMARYSleep is restorative, whereas reduced sleep leads to negative health outcomes, such as increased susceptibility to disease. Sleep deprivation tends to attenuate inflammatory responses triggered by infection or exposure to endotoxin, such as bacterial lipopolysaccharide (LPS). Previous studies have demonstrated that Siberian hamsters (Phodopus sungorus), photoperiodic rodents, attenuate LPS-induced fever, sickness behavior and upstream pro-inflammatory gene expression when adapted to short day lengths. Here, we tested whether manipulation of photoperiod alters the suppressive effects of sleep deprivation upon cytokine gene expression after LPS challenge. Male Siberian hamsters were adapted to long (16h:8h light:dark) or short (8h:16h light:dark) photoperiods for >10weeks, and were deprived of sleep for 24h using the multiple platform method or remained in their home cage. Hamsters received an intraperitoneal injection of LPS or saline (control) 18h after starting the protocol, and were killed 6h later. LPS increased liver and hypothalamic interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF) gene expression compared with vehicle. Among LPS-challenged hamsters, sleep deprivation reduced IL-1 mRNA levels in liver and hypothalamus, but not TNF. IL-1 attenuation was independent of circulating baseline cortisol, which did not increase after sleep deprivation. Conversely, photoperiod altered baseline cortisol, but not pro-inflammatory gene expression in sleep-deprived hamsters. These results suggest that neither photoperiod nor glucocorticoids influence the suppressive effect of sleep deprivation upon LPSinduced inflammation.

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“…When looking across species in which seasonally variable sickness responses have been documented, the common variable that predicts which season an animal will show reduced or enhanced sickness is the animal's body mass, not reproductive state or day length (Ashley and Wingfield, 2012;Carlton et al, 2012). Specifically, seasonally breeding animals show attenuated sickness responses to the bacterial mimetic lipopolysaccharide (LPS) in the season in which they have the lowest body mass , 2008.…”

Section: Introductionmentioning

confidence: 99%

Body mass affects seasonal variation in sickness intensity in a seasonally-breeding rodent

Carlton

Demas

2015

Journal of Experimental Biology

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Species that display seasonal variation in sickness intensity show the most intense response in the season during which they have the highest body mass, suggesting that sickness intensity may be limited by an animal's energy stores. Siberian hamsters (Phodopus sungorus) display lower body masses and less intense sickness when housed in short, winter-like days as opposed to long, summer-like days. To determine whether reduced sickness intensity displayed by short-day hamsters is a product of seasonal changes in body mass, we food restricted long-day hamsters so that they exhibited body mass loss that mimicked the natural photoperiod-induced loss of body mass in short-day hamsters. We then experimentally induced sickness with lipopolysaccharide (LPS) and compared sickness responses among long-day food-restricted and long-and short-day ad libitum fed groups, predicting that long-day food-restricted hamsters would show sickness responses comparable to those of short-day ad libitum fed hamsters and attenuated in comparison to long-day ad libitum fed hamsters. We found that long-day food-restricted hamsters showed attenuated LPSinduced anorexia, loss of body mass and hypothermia compared with long-day ad libitum fed animals; however, anorexia remained elevated in long-day food-restricted animals compared with short-day ad libitum fed animals. Additionally, LPS-induced anhedonia and decreases in nest building were not influenced by body mass. Results of hormone assays suggest that cortisol levels could play a role in the attenuation of sickness in long-day food-restricted hamsters, indicating that future research should target the roles of glucocorticoids and natural variation in energy stores in seasonal sickness variation.

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Leptin, a neuroendocrine mediator of immune responses, inflammation, and sickness behaviors

Cited by 74 publications

References 143 publications

Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

Sleep deprivation attenuates endotoxin-induced cytokine gene expression independent of day length and circulating cortisol in male Siberian hamsters (Phodopus sungorus)

Body mass affects seasonal variation in sickness intensity in a seasonally-breeding rodent

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