Hormone‐sensitive lipase (HSL) is also a retinyl ester hydrolase: evidence from mice lacking HSL

Ström, Kristoffer; Gundersen, Thomas E.; Hansson, Ola; Lucas, Stéphanie; Fernandez, Céline; Blomhoff, Rune; Holm, Cecilia

doi:10.1096/fj.08-120923

Cited by 82 publications

(78 citation statements)

References 43 publications

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“…[15][16][17][18][19][20][21][22][23][24] On the opposite, in the present study a three-fold excess of vitamin A intake in early life (day 1 to day 20 of life) exacerbated WAT expansion in response to a HF diet later in life. The reason(s) of this apparent discrepancy is unknown but could relate to concentration-dependent effects, because studies in adult animals typically used relatively high retinoid concentrations (reviewed in 10 ).…”

Section: Discussioncontrasting

confidence: 67%

“…9,10 Retinoic acid (RA), its acid form, potently blocks adipogenesis of cultured preadipose cells when introduced at early stages of the differentiation process, 11 although other reports indicate that RA at low doses may in fact promote adipogenesis. [12][13][14] Studies in adult rodents treated with RA [15][16][17][18][19][20][21][22][23] or retinaldehyde 24 sustain an antiadiposity action of vitamin A derivatives in vivo. Furthermore, results from animal studies 16,[25][26][27][28] and human observational studies 29,30 point to an inverse relationship between vitamin A status and body fat content.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin A supplementation in early life affects later response to an obesogenic diet in rats

et al. 2012

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OBJECTIVE:To assess the influence of supplementation with a moderate dose of vitamin A in early life on adipose tissue development and the response to an obesogenic diet later in life. METHODS: During the suckling period, rat pups received a daily oral dose of retinyl palmitate corresponding to three times the vitamin A ingested daily from maternal milk. Control rats received the vehicle (olive oil). Short-term effects of treatment on gene expression and morphology of white adipose tissue (WAT) were analyzed in animals on the day after weaning (day 21). To study long-term effects, control and vitamin A-treated rats were fed, after weaning, a normal fat or a high-fat (HF) diet for 16 weeks. RESULTS: WAT of vitamin A-treated young rats (day 21) was enriched in small adipocytes with a reduced expression of adipogenic markers (peroxisome proliferator-activated receptor g and lipoprotein lipase) and an increased cell proliferation potential as indicated by increased expression of proliferating cell nuclear antigen. Increased retinoic acid (RA)-induced transcriptional responses were present in the tissues of vitamin A-treated young rats (day 21) including WAT. Vitamin A-treated rats developed higher adiposity than control rats on a HF diet as indicated by body composition analysis and increased WAT depot mass, adipocyte diameter, WAT DNA content, leptinemia and adipose leptin gene expression. Excess adiposity gain in vitamin A-treated rats developed in the absence of changes in body weight and was attributable to excess adipocyte hyperplasia. No differences in adiposity were observed between vitamin A-treated rats and control rats on a normal fat diet. Total retinol levels in WAT of vitamin A-treated rats were elevated at weaning (day 21) and normalized by day 135 of age. CONCLUSION: Vitamin A intake in the early stages of postnatal life favors subsequent HF diet-induced adiposity gain through mechanisms that may relate to changes in adipose tissue development, likely mediated by RA.

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Section: Discussioncontrasting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Vitamin A supplementation in early life affects later response to an obesogenic diet in rats

et al. 2012

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“…HSL-stimulated lipolysis results in the liberation of free fatty acids, including palmitate from triglycerides in adipocytes (13,29,44). Palmitate treatment enhanced SphK1 expression in C2C12 myotubes (45).…”

Section: Discussionmentioning

confidence: 99%

Adipocyte Lipolysis-stimulated Interleukin-6 Production Requires Sphingosine Kinase 1 Activity

Zhang

Mottillo

Zhao

et al. 2014

Journal of Biological Chemistry

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Background: Lipolysis contributes to adipose inflammation. Results: Lipolysis up-regulates sphingosine kinase 1 (SphK1) in adipocytes. Modulation of SphK1 regulates adipose lipolysisstimulated interleukin 6 production. Conclusion: SphK1 plays a pivotal role in adipose inflammation. Significance: Identification of a role for SphK1 in lipolysis-triggered adipose inflammation. Targeting SphK1 provides a novel intervention for adipose inflammation and associated metabolic syndromes.

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“…As in the liver, retinyl esters stored in adipose tissue can be mobilized and secreted back into the circulation bound to RBP4 synthesized in adipocytes ( 55,(128)(129)(130). These retinyl esters are fi rst hydrolyzed by hormone-sensitive lipase (HSL), which acts as a physiologically relevant REH in adipocytes ( 130,131 ). Mice lacking HSL expression are unable to hydrolyze adipocyte retinyl esters; this results in abnormal retinoid signaling, leading to aberrant adipocyte differentiation ( 131 ).…”

Section: Retinoids In Adipose Tissuementioning

confidence: 99%

Retinol and retinyl esters: biochemistry and physiology

O’Byrne

Blaner

2013

Journal of Lipid Research

311

250

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The different retinoid forms present within the body (see Fig. 1 ) are generated by and large through modifi cations to the terminal polar end group of the molecule. Retinol and retinyl esters are the most abundant retinoid forms present in the body. All-trans -retinol is by defi nition vitamin A. When a fatty acyl group is esterifi ed to the hydroxyl terminus of retinol, a storage form of retinol, the retinyl ester, is formed. The most abundant retinyl esters present in the body are those of palmitic acid, oleic acid, stearic acid, and linoleic acid ( 6, 7 ). Although retinyl acetate can be found in supplements to foods and vitamin formulations, only long-chain acyl groups are esterifi ed to retinol by animals. Retinyl esters have no known biological activity aside from retinol storage and for serving as the substrate for the formation of the visual chromophore 11-cis -retinal, which must be formed from all-trans -retinyl ester through linked hydrolysis and isomerization reactions catalyzed by the enzyme RPE65 ( 3,4,8,9 ). Retinol is a transport form and a precursor form, which is enzymatically activated to retinoic acid via a two-step oxidation process. The primary role of retinal is in the eye where 11-cis -retinal is needed for visual pigment formation. In tissues, retinal serves as an intermediate in the synthesis of retinoic acid from retinol ( 6, 7 ). The literature also suggests a direct role for retinal in adipose tissue, where it was shown to inhibit adipogenesis and suppress peroxisome proliferator-activated receptor-␥ (PPAR ␥ ) and retinoid X receptor (RXR) responses in cell culture models and in mouse models fed high-fat diets ( 10 ).Abstract By defi nition, a vitamin is a substance that must be obtained regularly from the diet. Vitamin A must be acquired from the diet, but unlike most vitamins, it can also be stored within the body in relatively high levels. For humans living in developed nations or animals living in present-day vivariums, stored vitamin A concentrations can become relatively high, reaching levels that can protect against the adverse effects of insuffi cient vitamin A dietary intake for six months, or even much longer. The ability to accumulate vitamin A stores lessens the need for routinely consuming vitamin A in the diet, and this provides a selective advantage to the organism. The molecular processes that underlie this selective advantage include effi cient mechanisms to acquire vitamin A from the diet, effi cient and overlapping mechanisms for the transport of vitamin A in the circulation, a specifi c mechanism allowing for vitamin A storage, and a mechanism for mobilizing vitamin A from these stores in response to tissue needs. These processes are considered in this review. Since the identifi cation of fat-soluble A a century ago ( 1 ), retinoids (vitamin A and its natural and synthetic analogs) have been the most extensively studied of the fatsoluble vitamins. This research has identifi ed essential roles for retinoids in many different aspects of mammalian physiology, includ...

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Hormone‐sensitive lipase (HSL) is also a retinyl ester hydrolase: evidence from mice lacking HSL

Cited by 82 publications

References 43 publications

Vitamin A supplementation in early life affects later response to an obesogenic diet in rats

Vitamin A supplementation in early life affects later response to an obesogenic diet in rats

Adipocyte Lipolysis-stimulated Interleukin-6 Production Requires Sphingosine Kinase 1 Activity

Retinol and retinyl esters: biochemistry and physiology

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