New players of the adipose secretome: Therapeutic opportunities and challenges

Voilquin, Laetitia; Dannieskiold-Samsøe, Niels Banhos; Zhao, Meng; Allen, Hobson; Svensson, Katrin J.

doi:10.1016/j.coph.2022.102302

Cited by 4 publications

(2 citation statements)

References 58 publications

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“…Alternatively, the thermogenic fat cells may have acted non-cell autonomously to remodel the adipose milieu in ways that limit immunocyte recruitment, reduce fibrosis, and promote insulin sensitivity 3,50 . Thermogenic fat cells can also engage in inter-organ signaling that improves glucose handling in distant organs 51 . In this regard, it is interesting to note that a SNP near the human RBM43 gene has been associated with type 2 diabetes in an African-American population 52 .…”

Section: Discussionmentioning

confidence: 99%

RBM43 links adipose inflammation and energy expenditure through translational regulation of PGC1α

Dumesic

Wilensky

Bose

et al. 2023

Preprint

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Adipose thermogenesis involves specialized mitochondrial function that counteracts metabolic disease through dissipation of chemical energy as heat. However, inflammation present in obese adipose tissue can impair oxidative metabolism. Here, we show that PGC1alpha, a key governor of mitochondrial biogenesis and thermogenesis, is negatively regulated at the level of mRNA translation by the little-known RNA-binding protein RBM43. Rbm43 is expressed selectively in white adipose depots that have low thermogenic potential, and is induced by inflammatory cytokines. RBM43 suppresses mitochondrial and thermogenic gene expression in a PGC1alpha-dependent manner and its loss protects cells from cytokine-induced mitochondrial impairment. In mice, adipocyte-selective Rbm43 disruption increases PGC1alpha translation, resulting in mitochondrial biogenesis and adipose thermogenesis. These changes are accompanied by improvements in glucose homeostasis during diet-induced obesity that are independent of body weight. The action of RBM43 suggests a translational mechanism by which inflammatory signals associated with metabolic disease dampen mitochondrial function and thermogenesis.

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Section: Discussionmentioning

confidence: 99%

RBM43 links adipose inflammation and energy expenditure through translational regulation of PGC1α

Dumesic

Wilensky

Bose

et al. 2023

Preprint

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“…28 Adipose Tissue: Strategic Networking Through a Diverse Secretome Distinct classes of bioactive molecules are released by the adipose tissue, including peptide hormones, cytokines, enzymes, complement factors, growth factors, and chemokines (collectively referred to here as "adipokines"), and bioactive lipids (known as "lipokines"), which influence the metabolic, inflammatory, and immune landscape in normal physiology and disease. 25,30,31 Therefore, an altered adipose tissue secretory profile can affect core physiologic processes, locally or systemically, through an intricate signaling communication network, which includes not only classical adipokines and lipokines but also other mediators released by the adipose tissue, such as metabolites, noncoding RNAs, and exosomes. 25,[32][33][34] At the center of the adipose tissue regulatory network, adipokines represent an expanding class of cell signaling molecules that play a key role in energy homeostasis, inflammation, and immune response.…”

Section: Effect Of Obesity On Tumor Biology Development Of Cancer And...mentioning

confidence: 99%

Effect of Obesity on the Pharmacokinetics and Pharmacodynamics of Anticancer Agents

Zamboni,

Charlab,

Burckart

et al. 2023

The Journal of Clinical Pharma

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An objective of the Precision Medicine Initiative, launched in 2015 by the US Food and Drug Administration and National Institutes of Health, is to optimize and individualize dosing of drugs, especially anticancer agents, with high pharmacokinetic and pharmacodynamic variability. The American Society of Clinical Oncology recently reported that 40% of obese patients receive insufficient chemotherapy doses and exposures, which may lead to reduced efficacy, and recommended pharmacokinetic studies to guide appropriate dosing in these patients. These issues will only increase in importance as the incidence of obesity in the population increases. This publication reviews the effects of obesity on (1) tumor biology, development of cancer, and antitumor response; (2) pharmacokinetics and pharmacodynamics of small‐molecule anticancer drugs; and (3) pharmacokinetics and pharmacodynamics of complex anticancer drugs, such as carrier‐mediated agents and biologics. These topics are not only important from a scientific research perspective but also from a drug development and regulator perspective. Thus, it is important to evaluate the effects of obesity on the pharmacokinetics and pharmacodynamics of anticancer agents in all categories of body habitus and especially in patients who are obese and morbidly obese. As the effects of obesity on the pharmacokinetics and pharmacodynamics of anticancer agents may be highly variable across drug types, the optimal dosing metric and algorithm for difference classes of drugs may be widely different. Thus, studies are needed to evaluate current and novel metrics and methods for measuring body habitus as related to optimizing the dose and reducing pharmacokinetic and pharmacodynamic variability of anticancer agents in patients who are obese and morbidly obese.

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Editorial overview: New and revitalized old targets in metabolic disease

Hansen,

Novak

2024

Current Opinion in Pharmacology

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New players of the adipose secretome: Therapeutic opportunities and challenges

Cited by 4 publications

References 58 publications

RBM43 links adipose inflammation and energy expenditure through translational regulation of PGC1α

RBM43 links adipose inflammation and energy expenditure through translational regulation of PGC1α

Effect of Obesity on the Pharmacokinetics and Pharmacodynamics of Anticancer Agents

Editorial overview: New and revitalized old targets in metabolic disease

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