Retinoic acid and vitamin D(3) powerfully inhibit in vitro leptin secretion by human adipose tissue

Leptin, the product of the ob gene, is secreted into the circulation by white adipose tissue; its major role being to participate in the regulation of energy homeostasis. Plasma leptin levels are mainly determined by the relative adiposity of the subject; however, the great dispersion of values for any given body mass index and the noteworthy gender-based differences indicate that other factors are operating. Steroid hormones actively participate in the regulation of leptin secretion; however, non-steroid nuclear hormones have either not been studied or have provided contradictory results. In order to understand the role of hormones of the non-steroid superfamily such as 3,5,3'-tri-iodothyronine (T(3)), vitamin D(3) and retinoic acid (RA) in the control of leptin secretion, in the present work doses of 10(-9), 10(-8) and 10(-7) M of these compounds have been studied on in vitro leptin secretion. The organ culture was performed with omental adipose tissue samples from healthy donors (n=28). T(3) was devoid of effect at any dose studied, while an inhibition of leptin secretion was observed with 9-cis-RA (slight) and all-trans-RA (potent). Interestingly, vitamin D(3) exerted a powerfully inhibitory role at the doses studied, and its action was synergistic with all-trans-RA. In conclusion, in vitro leptin secretion by human adipose tissue is negatively controlled by either RA or vitamin D(3). The clinical significance of leptin regulation by this superfamily of nuclear receptors remains to be ascertained.

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TSH stimulates leptin secretion by a direct effect on adipocytes

Journal of Endocrinology ◽

10.1677/joe.0.1760007 ◽

2003 ◽

Vol 176 (1) ◽

pp. 7-12 ◽

Cited By ~ 81

Author(s):

C Menendez ◽

R Baldelli ◽

JP Camina ◽

B Escudero ◽

R Peino ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Homeostasis ◽

Direct Action ◽

Human Adipose Tissue ◽

Pituitary Hormones ◽

Organ Cultures ◽

Omental Adipose Tissue ◽

Thyroid Axis ◽

The Central Nervous System

Leptin is a circulating hormone secreted by adipose tIssue which acts as a signal to the central nervous system where it regulates energy homeostasis and neuroendocrine processes. Although leptin modulates the secretion of several pituitary hormones, no information is available regarding a direct action of pituitary products on leptin release. However, it has been pointed out that leptin and TSH have a coordinated pulsatility in plasma. In order to test a direct action of TSH on in vitro leptin secretion, a systematic study of organ cultures of human omental adipose tIssue was performed in samples obtained at surgery from 34 patients of both sexes during elective abdominal surgery. TSH powerfully stimulated leptin secretion by human adipose tIssue in vitro. In contrast, prolactin, ACTH, FSH and LH were devoid of action. These results suggest that leptin and the thyroid axis maintain a complex and dual relationship and open the possibility that plasmatic changes in TSH may contribute to the regulation of leptin pulses.

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Release of Inflammatory Mediators by Human Adipose Tissue Is Enhanced in Obesity and Primarily by the Nonfat Cells: A Review

Mediators of Inflammation ◽

10.1155/2010/513948 ◽

2010 ◽

Vol 2010 ◽

pp. 1-20 ◽

Cited By ~ 120

Author(s):

John N. Fain

Keyword(s):

Adipose Tissue ◽

In Vitro Release ◽

Human Adipose Tissue ◽

Fat Cells ◽

Omental Adipose Tissue ◽

Subcutaneous Adipose ◽

Circulating Levels ◽

Pai 1

This paper considers the role of putative adipokines that might be involved in the enhanced inflammatory response of human adipose tissue seen in obesity. Inflammatory adipokines [IL-6, IL-10, ACE, TGFβ1, TNFα, IL-1β, PAI-1, and IL-8] plus one anti-inflammatory [IL-10] adipokine were identified whose circulating levels as well as in vitro release by fat are enhanced in obesity and are primarily released by the nonfat cells of human adipose tissue. In contrast, the circulating levels of leptin and FABP-4 are also enhanced in obesity and they are primarily released by fat cells of human adipose tissue. The relative expression of adipokines and other proteins in human omental as compared to subcutaneous adipose tissue as well as their expression in the nonfat as compared to the fat cells of human omental adipose tissue is also reviewed. The conclusion is that the release of many inflammatory adipokines by adipose tissue is enhanced in obese humans.

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Vitamin D alleviates oxidative stress in adipose tissue and mesenteric vessels from obese patients with subclinical inflammation

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0340 ◽

2020 ◽

Vol 98 (2) ◽

pp. 85-92 ◽

Cited By ~ 1

Author(s):

Mihaela Ionica ◽

Oana M. Aburel ◽

Adrian Vaduva ◽

Alexandra Petrus ◽

Sonia Rațiu ◽

...

Keyword(s):

Oxidative Stress ◽

Vitamin D ◽

Adipose Tissue ◽

Vascular Function ◽

Ex Vivo ◽

Active Form ◽

Reactive Oxygen Species Generation ◽

Obese Patients ◽

Tissue Samples

Obesity is an age-independent, lifestyle-triggered, pandemic disease associated with both endothelial and visceral adipose tissue (VAT) dysfunction leading to cardiometabolic complications mediated via increased oxidative stress and persistent chronic inflammation. The purpose of the present study was to assess the oxidative stress in VAT and vascular samples and the effect of in vitro administration of vitamin D. VAT and mesenteric artery branches were harvested during abdominal surgery performed on patients referred for general surgery (n = 30) that were randomized into two subgroups: nonobese and obese. Serum levels of C-reactive protein (CRP) and vitamin D were measured. Tissue samples were treated or not with the active form of vitamin D: 1,25(OH)2D3 (100 nmol/L, 12 h). The main findings are that in obese patients, (i) a low vitamin D status was associated with increased inflammatory markers and reactive oxygen species generation in VAT and vascular samples and (ii) in vitro incubation with vitamin D alleviated oxidative stress in VAT and vascular preparations and also improved the vascular function. We report here that the serum level of vitamin D is inversely correlated with the magnitude of oxidative stress in the adipose tissue. Ex vivo treatment with active vitamin D mitigated obesity-related oxidative stress.

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Gender Differences in Both Spontaneous and Stimulated Leptin Secretion by Human Omental Adipose Tissue in Vitro: Dexamethasone and Estradiol Stimulate Leptin Release in Women, But Not in Men1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.6.4849 ◽

1998 ◽

Vol 83 (6) ◽

pp. 2149-2155 ◽

Cited By ~ 1

Author(s):

Xesús Casabiell ◽

Verónica Piñeiro ◽

Roberto Peino ◽

Mary Lage ◽

Jesús Camiña ◽

...

Keyword(s):

Gender Differences ◽

Adipose Tissue ◽

Energy Homeostasis ◽

Tissue Sample ◽

Intrinsic Property ◽

Secretory Activity ◽

Omental Adipose Tissue ◽

Adipose Tissue In Vitro ◽

Human Omental Adipose Tissue

Leptin is a hormone secreted by the adipocytes to serve as a signal to the central nervous system to regulate energy homeostasis. Circulating leptin mainly reflects both total fat mass and the size of constituent adipocytes, although other ancillary hormonal factors may contribute to its blood concentration. Relevant gender differences in leptin concentrations have been reported, but it is not clear whether the elevated leptin levels in women are an intrinsic property of their adipocytes or merely reflect a greater amount of fat reserves. To clarify these points, a systematic study with organ culture from human omental adipose tissue either stimulated or not with steroid hormones was undertaken in samples obtained at surgery from 67 nonobese donors (33 women and 34 men). The assay was standardized in periods of 24 h ending at 96 h, with no apparent tissue damage. Each adipose tissue sample from a single donor was incubated in triplicate, and leptin results are expressed as the mean ± sem of the integrated secretion to the medium (area under the curve; nanograms of leptin per g tissue/48 h). Control nonstimulated samples showed a steady leptin secretion along the 96 h studied, with the peak of secretory activity reached at 48 h; afterward, the in vitro secretion reached a plateau state. Spontaneous leptin secretion in samples from 33 women (3904 ± 347) was significantly higher (P < 0.05) than that in samples from 34 men (2940 ± 323). Coincubation of adipose tissue with 1 μmol/L dexamethasone induced a clear-cut leptin increase (P < 0.05) in samples from women (5848 ± 624; n = 12), but did not change the spontaneous release of leptin in samples from men (3353 ± 741; n = 6). Similarly, coincubation of adipose tissue with 1 μmol/L estradiol induced a notable leptin increase (P < 0.05) in samples from women (5698 ± 688; n = 9), whereas it did not alter the secretion in the male samples (3373 ± 444; n = 6). In samples from both sexes, coincubation with 1 μmol/L estrone or progesterone had no effect, whereas 1 μmol/L forskolin significantly (P < 0.05) reduced leptin release. In conclusion, leptin secretion from omental adipose tissue in vitro 1) is significantly higher in samples from women than in samples from men, 2) is stimulated by dexamethasone and estradiol in women but not in men, 3) is not modified by progesterone or estrone in both sexes, and 4) is inhibited by forskolin in both genders. This different response to the stimulation of adipose tissue may be the biological basis for the gender differences observed in circulating levels of human leptin.

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Dihydrotestosterone, stanozolol, androstenedione and dehydroepiandrosterone sulphate inhibit leptin secretion in female but not in male samples of omental adipose tissue in vitro: lack of effect of testosterone

Journal of Endocrinology ◽

10.1677/joe.0.1600425 ◽

1999 ◽

Vol 160 (3) ◽

pp. 425-432 ◽

Cited By ~ 37

Author(s):

V Pineiro ◽

X Casabiell ◽

R Peino ◽

M Lage ◽

JP Camina ◽

...

Keyword(s):

Adipose Tissue ◽

In Vitro Study ◽

Significant Inhibition ◽

Dehydroepiandrosterone Sulphate ◽

Organ Cultures ◽

Omental Adipose Tissue ◽

The Central Nervous System ◽

The Mean ◽

Gender Based

Leptin, the product of the Ob gene, is a polypeptide hormone expressed in adipocytes which acts as a signalling factor from the adipose tissue to the central nervous system, regulating food intake and energy expenditure. It has been reported that circulating leptin levels are higher in women than in men, even after correction for body fat. This gender-based difference may be conditioned by differences in the levels of androgenic hormones. To explore this possibility, a systematic in vitro study with organ cultures from human omental adipose tissue, either stimulated or not with androgens (1 microM), was undertaken in samples obtained from surgery on 44 non-obese donors (21 women and 23 men). The assay was standardized in periods of 24 h, ending at 96 h, with no apparent tissue damage. Leptin results are expressed as the mean+/-s.e.m. of the integrated secretion into the medium, expressed as ng leptin/g tissue per 48 h. Spontaneous leptin secretion in samples from female donors (4149+/-301) was significantly higher (P<0.01) than that from male donors (2456+/-428). Testosterone did not exert any significant effect on in vitro leptin secretion in either gender (4856+/-366 in women, 3322+/-505 in men). Coincubation of adipose tissue with dihydrotestosterone (DHT) induced a significant (P<0.05) leptin decrease in samples taken from women (3119+/-322) but not in those taken from men (2042+/-430). Stanozolol, a non-aromatizable androgen, decreased (P<0.05) leptin secretion in female samples (2809+/-383) but not in male (1553+/-671). Dehydroepiandrosterone sulphate (DHEA-S) induced a significant (P<0.01) leptin decrease in female samples (2996+/-473), with no modifications in samples derived from males (1596+/-528). Exposure to androstenedione also resulted in a significant reduction (P<0.01) of leptin secretion in samples taken from women (2231+/-264), with no effect on male adipose tissue (1605+/-544). In conclusion, DHT, stanozolol, DHEA-S and androstenedione induced a significant inhibition of in vitro leptin secretion in samples from female donors, without affecting the secretion in samples from men. Testosterone was devoid of activity in either gender.

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IN VITRO STUDIES ON LIPOLYSIS IN HUMAN ADIPOSE TISSUE

Acta Endocrinologica ◽

10.1530/acta.0.061s156 ◽

1969 ◽

Vol 61 (1_Suppl) ◽

pp. S156

Author(s):

Suad Efendić ◽

Peter Amer ◽

Jan Östman

Keyword(s):

Adipose Tissue ◽

Human Adipose Tissue ◽

In Vitro Studies

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Adipose Tissue Remodeling by Prolonged Administration of High Dose of Vitamin D3 in Rats Treated to Prevent Sarcopenia

Revista de Chimie ◽

10.37358/rc.17.9.5842 ◽

2017 ◽

Vol 68 (9) ◽

pp. 2139-2143 ◽

Cited By ~ 1

Author(s):

Alin Constantin Pinzariu ◽

Sorin Aurelian Pasca ◽

Allia Sindilar ◽

Cristian Drochioi ◽

Mihail Balan ◽

...

Keyword(s):

Vitamin D ◽

Adipose Tissue ◽

Vitamin D3 ◽

Term Treatment ◽

High Dose ◽

Omental Adipose Tissue ◽

Long Term Treatment ◽

Male Wistar Rats ◽

Adipose Tissue Remodeling ◽

Visceral Adipose

To examine the effect of high dose vitamin D3 treatment on visceral adipose tissue, we used vitamin D deficient male Wistar rats (18 months old) as a model of sarcopenia. The aging process is not only responsive for the losing muscle mass but also for redistribution of lipid resulting in altered fatty acid storage and dysdifferentiation of mesenchymal precursors. The effect of aging and vitamin D treatment (weekly oral gavage with 0.125 mg vitamin D3 (5000 IU)/100g body weight) on the omental adipose tissue were histological examinated. At the end of the experiment (9 monhs), adaptive changes to the reduction of adipogenesis and increased apoptosis in response to long-term treatment with vitamin D consisted of smaller size of adipocyte and moderate macrophage infiltrate.

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Long-Term Severe In Vitro Hypoxia Exposure Enhances the Vascularization Potential of Human Adipose Tissue-Derived Stromal Vascular Fraction Cell Engineered Tissues

International Journal of Molecular Sciences ◽

10.3390/ijms22157920 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7920

Author(s):

Myroslava Mytsyk ◽

Giulia Cerino ◽

Gregory Reid ◽

Laia Gili Sole ◽

Friedrich S. Eckstein ◽

...

Keyword(s):

Adipose Tissue ◽

Therapeutic Potential ◽

Stromal Vascular Fraction ◽

Human Adipose Tissue ◽

Bioreactor Culture ◽

Proliferating Cells ◽

Angiogenic Potential ◽

Engineered Tissues

The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.

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Signal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes

Antioxidants ◽

10.3390/antiox10020334 ◽

2021 ◽

Vol 10 (2) ◽

pp. 334

Author(s):

Aisha Y. Madani ◽

Yasser Majeed ◽

Houari B. Abdesselem ◽

Maha V. Agha ◽

Muneera Vakayil ◽

...

Keyword(s):

Adipose Tissue ◽

Molecular Mechanisms ◽

Adenosine Monophosphate ◽

Human Adipose Tissue ◽

Premature Aging ◽

Guanosine Monophosphate ◽

Negative Regulator ◽

Signal Transducer ◽

Interferon Signaling

Obesity promotes premature aging and dysfunction of white adipose tissue (WAT) through the accumulation of cellular senescence. The senescent cells burden in WAT has been linked to inflammation, insulin-resistance (IR), and type 2 diabetes (T2D). There is limited knowledge about molecular mechanisms that sustain inflammation in obese states. Here, we describe a robust and physiologically relevant in vitro system to trigger senescence in mouse 3T3-L1 preadipocytes. By employing transcriptomics analyses, we discovered up-regulation of key pro-inflammatory molecules and activation of interferon/signal transducer and activator of transcription (STAT)1/3 signaling in senescent preadipocytes, and expression of downstream targets was induced in epididymal WAT of obese mice, and obese human adipose tissue. To test the relevance of STAT1/3 signaling to preadipocyte senescence, we used Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9) technology to delete STAT1/3 and discovered that STAT1 promoted growth arrest and cooperated with cyclic Guanosine Monophosphate-Adenosine Monophosphate (GMP-AMP) synthase-stimulator of interferon genes (cGAS-STING) to drive the expression of interferon β (IFNβ), C-X-C motif chemokine ligand 10 (CXCL10), and interferon signaling-related genes. In contrast, we discovered that STAT3 was a negative regulator of STAT1/cGAS-STING signaling—it suppressed senescence and inflammation. These data provide insights into how STAT1/STAT3 signaling coordinates senescence and inflammation through functional interactions with the cGAS/STING pathway.

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