Determination of the half-life of circulating leptin in the mouse

Burnett, Lisa C.; Skowronski, Alicja A.; Rausch, Richard; LeDuc, Charles A.; Leibel, Rudolph L.

doi:10.1038/ijo.2016.238

Cited by 29 publications

(24 citation statements)

References 52 publications

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“…Co, control; SN, supernatant. regulate leptin on a posttranscriptional level, whereas the long-term nutritional status affects leptin mRNA expression (31). In the past, several IL-6-type cytokines were suggested to affect leptin production or proposed as potential targets to treat obesity (5)(6)(7)(8)28).…”

Section: Discussionmentioning

confidence: 99%

IL-6–Type Cytokine Signaling in Adipocytes Induces Intestinal GLP-1 Secretion

et al. 2017

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We recently showed that interleukin (IL)-6-type cytokine signaling in adipocytes induces free fatty acid release from visceral adipocytes, thereby promoting obesity-induced hepatic insulin resistance and steatosis. In addition, IL-6-type cytokines may increase the release of leptin from adipocytes and by those means induce glucagon-like peptide 1 (GLP-1) secretion. We thus hypothesized that IL-6-type cytokine signaling in adipocytes may regulate insulin secretion. To this end, mice with adipocyte-specific knockout of gp130, the signal transducer protein of IL-6, were fed a high-fat diet for 12 weeks. Compared with control littermates, knockout mice showed impaired glucose tolerance and circulating leptin, GLP-1, and insulin levels were reduced. In line, leptin release from isolated adipocytes was reduced, and intestinal proprotein convertase subtilisin/kexin type 1 () expression, the gene encoding PC1/3, which controls GLP-1 production, was decreased in knockout mice. Importantly, treatment with the GLP-1 receptor antagonist exendin 9-39 abolished the observed difference in glucose tolerance between control and knockout mice. Ex vivo, supernatant collected from isolated adipocytes of gp130 knockout mice blunted expression and GLP-1 release from GLUTag cells. In contrast, glucose- and GLP-1-stimulated insulin secretion was not affected in islets of knockout mice. In conclusion, adipocyte-specific IL-6 signaling induces intestinal GLP-1 release to enhance insulin secretion, thereby counteracting insulin resistance in obesity.

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Section: Discussionmentioning

confidence: 99%

IL-6–Type Cytokine Signaling in Adipocytes Induces Intestinal GLP-1 Secretion

et al. 2017

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“…22,23,63 For spike, LFP, and fiber photometry recordings, control signals were recorded prior to leptin administration. 22,23,63 For spike, LFP, and fiber photometry recordings, control signals were recorded prior to leptin administration.…”

Section: Chemicals and Odor Stimulation During In Vivo Recordingsmentioning

confidence: 99%

“…For leptin injections (in behavioral experiments and in vivo spike, LFP, and fiber photometry recordings), leptin (mouse recombinant leptin, L3772, purchased from Sigma-Aldrich, USA) was dissolved in normal saline at a concentration of 0.5 mg/mL and injected ip at a dose of 1 μg/g body weight. 22,23,63 For spike, LFP, and fiber photometry recordings, control signals were recorded prior to leptin administration. Leptin was administered immediately after completion of the control recordings.…”

Section: Chemicals and Odor Stimulation During In Vivo Recordingsmentioning

confidence: 99%

Leptin modulates olfactory discrimination and neural activity in the olfactory bulb

Sun

Ke-ke

et al. 2019

Acta Physiologica

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Aim Leptin is an important peptide hormone that regulates food intake and plays a crucial role in modulating olfactory function. Although a few previous studies have investigated the effect of leptin on odor perception and discrimination in rodents, research on the neural basis underlying the behavioral changes is lacking. Here we study how leptin affects behavioral performance during a go/no‐go task and how it modulates neural activity of mitral/tufted cells in the olfactory bulb, which plays an important role in odor information processing and representation. Methods A go/no‐go odor discrimination task was used in the behavioral test. For in vivo studies, single unit recordings, local field potential recordings and fiber photometry recordings were used. For in vitro studies, we performed patch clamp recordings in the slice of the olfactory bulb. Results Behaviorally, leptin affects performance and reaction time in a difficult odor‐discrimination task. Leptin decreases the spontaneous firing of single mitral/tufted cells, decreases the odor‐evoked beta and high gamma local field potential response, and has bidirectional effects on the odor‐evoked responses of single mitral/tufted cells. Leptin also inhibits the population calcium activity in genetically identified mitral/tufted cells and granule cells. Furthermore, in vitro slice recordings reveal that leptin inhibits mitral cell activity through direct modulation of the voltage‐sensitive potassium channel. Conclusions The behavioral reduction in odor discrimination observed after leptin administration is likely due to decreased neural activity in mitral/tufted cells, caused by modulation of potassium channels in these cells.

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“…Data on the half-life of leptin in circulation is variable. In the mice the half-life of exogenously administered leptin was estimated to be about 40 minutes [82]. Whereas in humans the half-life of leptin in the circulation has been estimated to be between 20-30 minutes and is independent of adiposity [83].…”

Section: Elimination Of Leptinmentioning

confidence: 99%

Leptin: a pleitropic factor in physiology

Almabhouh¹,

Muhammad²,

Ibrahim³

et al. 2019

JCHS

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Leptin, a 16 kDa protein and a product of the ob/ob gene, has a tertiary structure similar to that of a cytokine. It is primarily secreted by white adipose tissue and its levels in the blood correlate positively with percentage body fat. Leptin was first identified in 1994 as a major factor that regulated food intake and energy balance. Leptin in the circulation exists either as a free monomeric hormone or bound to its soluble receptor. Its serum levels usually range from 0.5 to 37.7 ng/ml in males and 2.0 to 45.2 ng/ml in females. The half-life of leptin is between 20 - 30 minutes and it is eliminated mainly by the kidneys. However, research over the last 25 years has revealed numerous other physiological roles for leptin, including roles in inflammation, immune function, neuro-endocrine function, bone metabolism, blood pressure regulation and sexual maturation. Most of these roles have been identified from studies on leptin deficient rodents. Apart from energy balance and sexual maturation, where its role is direct and obvious, its actions on the rest of the other systems are permissive. Actions of leptin are both centrally and peripherally mediated involving receptors that are widely distributed in the body. Six leptin receptor isoforms, belonging to the class 1 cytokine receptor family, have been identified. These receptors are products of the OBR gene. The cellular actions of leptin are mediated through any one of five different signalling pathways that include the JAK-STAT, PI3K, MAPK, AMPK, and the mTOR signalling pathways.

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Determination of the half-life of circulating leptin in the mouse

Cited by 29 publications

References 52 publications

IL-6–Type Cytokine Signaling in Adipocytes Induces Intestinal GLP-1 Secretion

IL-6–Type Cytokine Signaling in Adipocytes Induces Intestinal GLP-1 Secretion

Leptin modulates olfactory discrimination and neural activity in the olfactory bulb

Leptin: a pleitropic factor in physiology

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