Role of myeloid cell leptin signaling in the regulation of glucose metabolism

Pereira, Sandra; Cline, Daemon L.; Chan, M.K.H.; Chai, Kalin; Yoon, Ji Soo; O’Dwyer, Shannon; Ellis, Cara; Glavas, Maria M.; Webber, Travis D.; Baker, Robert K.; Erener, Süheda; Covey, Scott D.; Kieffer, Timothy J.

doi:10.1038/s41598-021-97549-0

Cited by 4 publications

(3 citation statements)

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“…Furthermore, IL-1 receptor I deficient mice have improved glucose tolerance and reduced inflammation in obesity, suggesting that macrophage production of IL-1β is a critical inflammatory driver in obesity [ 39 ]. A study investigating the role of leptin signaling in myeloid cells found that specific deletion of leptin receptor in myeloid cells did not significantly affect glycemic control [ 41 ]. However, selective reconstitution of leptin receptor in myeloid cells in mice that were otherwise leptin receptor deficient resulted in improved glucose tolerance.…”

Section: Discussionmentioning

confidence: 99%

Effects of T cell leptin signaling on systemic glucose tolerance and T cell responses in obesity

et al. 2023

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Background/Objectives Leptin is an adipokine secreted in proportion to adipocyte mass and is therefore increased in obesity. Leptin signaling has been shown to directly promote inflammatory T helper 1 (Th1) and T helper 17 (Th17) cell number and function. Since T cells have a critical role in driving inflammation and systemic glucose intolerance in obesity, we sought to determine the role of leptin signaling in this context. Methods Male and female T cell-specific leptin receptor knockout mice and littermate controls were placed on low-fat diet or high-fat diet to induce obesity for 18 weeks. Weight gain, serum glucose levels, systemic glucose tolerance, T cell metabolism, and T cell differentiation and cytokine production were examined. Results In both male and female mice, T cell-specific leptin receptor deficiency did not reverse impaired glucose tolerance in obesity, although it did prevent impaired fasting glucose levels in obese mice compared to littermate controls, in a sex dependent manner. Despite these minimal effects on systemic metabolism, T cell-specific leptin signaling was required for changes in T cell metabolism, differentiation, and cytokine production observed in mice fed high-fat diet compared to low-fat diet. Specifically, we observed increased T cell oxidative metabolism, increased CD4+ T cell IFN-γ expression, and increased proportion of T regulatory (Treg) cells in control mice fed high-fat diet compared to low-fat diet, which were not observed in the leptin receptor conditional knockout mice, suggesting that leptin receptor signaling is required for some of the inflammatory changes observed in T cells in obesity. Conclusions T cell-specific deficiency of leptin signaling alters T cell metabolism and function in obesity but has minimal effects on obesity-associated systemic metabolism. These results suggest a redundancy in cytokine receptor signaling pathways in response to inflammatory signals in obesity.

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Section: Discussionmentioning

confidence: 99%

Effects of T cell leptin signaling on systemic glucose tolerance and T cell responses in obesity

et al. 2023

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“…Therefore, a glucometer type should be used consistently in a given experiment ( Ayala et al 2010 , Togashi et al 2016 ) and its results are usually most reliable when glycemia is not excessively high ( Togashi et al 2016 , Morley et al 2018 ). When doing GTTs and PTTs in models of diabetes, plasma glucose concentrations can be determined after completion of the tests using a glucose assay kit ( Pereira et al 2021 ).…”

Section: Factors To Consider When Assessing Glucose Metabolism ...mentioning

confidence: 99%

“…Sex hormones also affect body composition (amount and distribution of fat tissue), which is an important determinant of insulin sensitivity ( Elbers et al 1999 , Macotela et al 2009 , Hocking et al 2013 ). The enhanced insulin sensitivity associated with being female often deteriorates in insulin-resistant states ( Tramunt et al 2020 , Pereira et al 2021 ).…”

Section: Factors To Consider When Assessing Glucose Metabolism ...mentioning

confidence: 99%

In vivo techniques for assessment of insulin sensitivity and glucose metabolism

Hahn,

Giacca,

Pereira

2024

Journal of Endocrinology

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Metabolic tests are vital to determine in vivo insulin sensitivity and glucose metabolism in preclinical models, usually rodents. Such tests include glucose tolerance tests, insulin tolerance tests, and glucose clamps. Although these tests are not standardized, there are general guidelines for their completion and analysis that are constantly being refined. In this review, we describe metabolic tests in rodents as well as factors to consider when designing and performing them.

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