Acute retinol mobilization by retinol-binding protein 4 in mouse liver induces fibroblast growth factor 21 expression

Steinhoff, Julia; Wagner, Carina; Taschler, Ulrike; Wulff, Sascha; Kiefer, Marie F.; Petricek, Konstantin M.; Wowro, Sylvia J.; Oster, Moritz; Flores, Roberto E.; Yang, Na; Li, Chen; Meng, Yueming; Sommerfeld, Manuela; Weger, Stefan; Henze, Andrea; Raila, Jens; Lass, Achim; Schupp, Michael

doi:10.1016/j.jlr.2022.100268

Journal of Lipid Research

2022

DOI: 10.1016/j.jlr.2022.100268

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Acute retinol mobilization by retinol-binding protein 4 in mouse liver induces fibroblast growth factor 21 expression

Julia Steinhoff

Carina Wagner²,

Ulrike Taschler³

et al.

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2024

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Cited by 2 publications

References 64 publications

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Adipocyte HSL is required for maintaining circulating vitamin A and RBP4 levels during fasting

Steinhoff,

Wagner,

Dähnhardt

et al. 2024

EMBO Rep

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Vitamin A (retinol) is distributed via the blood bound to its specific carrier protein, retinol-binding protein 4 (RBP4). Retinol-loaded RBP4 is secreted into the circulation exclusively from hepatocytes, thereby mobilizing hepatic retinoid stores that represent the major vitamin A reserves in the body. The relevance of extrahepatic retinoid stores for circulating retinol and RBP4 levels that are usually kept within narrow physiological limits is unknown. Here, we show that fasting affects retinoid mobilization in a tissue-specific manner, and that hormone-sensitive lipase (HSL) in adipose tissue is required to maintain serum concentrations of retinol and RBP4 during fasting in mice. We found that extracellular retinol-free apo-RBP4 induces retinol release by adipocytes in an HSL-dependent manner. Consistently, global or adipocyte-specific HSL deficiency leads to an accumulation of retinoids in adipose tissue and a drop of serum retinol and RBP4 during fasting, which affects retinoid-responsive gene expression in eye and kidney and lowers renal retinoid content. These findings establish a novel crosstalk between liver and adipose tissue retinoid stores for the maintenance of systemic vitamin A homeostasis during fasting.

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Adipocyte HSL is required for maintaining circulating vitamin A and RBP4 levels during fasting

Steinhoff,

Wagner,

Dähnhardt

et al. 2024

EMBO Rep

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Intestinal retinol saturase is implicated in the development of obesity and epithelial homeostasis upon injury

Kiefer,

Meng,

Yang

et al. 2024

American Journal of Physiology-Endocrinology and Metabolism

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Retinol saturase (RetSat) is an oxidoreductase involved in lipid metabolism and the cellular sensitivity to peroxides. RetSat is highly expressed in metabolic organs like liver and adipose tissue and its global loss in mice increases body weight and adiposity. The regulation of RetSat expression and its function in the intestine are unexplored. Here, we show that RetSat is present in different segments of the digestive system, localizes to intestinal epithelial cells, and is upregulated by feeding mice high-fat diet (HFD). Intestine-specific RetSat deletion in adult mice did not affect nutrient absorption and energy homeostasis basally, but lowered body weight gain and fat mass of HFD-fed mice, potentially via increasing locomotor activity. Moreover, jejunal expression of genes related to β-oxidation and cholesterol efflux were decreased and colonic cholesterol content reduced upon RetSat deletion. In colitis, which we show to downregulate intestinal RetSat expression in humans and mice, RetSat ablation improved epithelial architecture of the murine colon. Thus, intestinal RetSat expression is regulated by dietary interventions and inflammation, and its loss reduces weight gain upon HFD-feeding and alleviates epithelial damage upon injury.

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Acute retinol mobilization by retinol-binding protein 4 in mouse liver induces fibroblast growth factor 21 expression

Cited by 2 publications

References 64 publications

Adipocyte HSL is required for maintaining circulating vitamin A and RBP4 levels during fasting

Adipocyte HSL is required for maintaining circulating vitamin A and RBP4 levels during fasting

Intestinal retinol saturase is implicated in the development of obesity and epithelial homeostasis upon injury

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