scholarly journals An RNAi screening of clinically relevant transcription factors regulating human adipogenesis and adipocyte metabolism

Endocrinology ◽  
2021 ◽  
Author(s):  
Christel Björk ◽  
Narmadha Subramanian ◽  
Jianping Liu ◽  
Juan Ramon Acosta ◽  
Beatriz Tavira ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Transcription Factors ◽  
Rnai Screen ◽  
Metabolic Phenotype ◽  
Cell Phenotype ◽  
Fat Cells ◽  
Fat Cell ◽  
Rnai Screening ◽  
Metabolic Conditions

Abstract Objective Healthy hyperplasic (many but smaller fat cells) white adipose tissue (WAT) expansion is mediated by recruitment, proliferation and/or differentiation of new fat cells. This process (adipogenesis) is controlled by transcriptional programs mostly identified in rodents. A systemic investigation of adipogenic human transcription factors (TFs) that are relevant for metabolic conditions has not been revealed previously. Methods TFs regulated in WAT by obesity, adipose morphology, cancer cachexia and insulin resistance were selected from microarrays. Their role in differentiation of human adipose tissue-derived stem cells (hASC) was investigated by RNA interference (RNAi) screen. Lipid accumulation, cell number and lipolysis were measured for all screened factors (148 TFs). RNA (RNAseq), protein (western blot) expression, insulin and catecholamine responsiveness were examined in hASC following siRNA treatment of selected target TFs. Results Analysis of TFs regulated by metabolic conditions in human WAT revealed that many of them belong to adipogenesis-regulating pathways. The RNAi screen identified 39 genes that affected fat cell differentiation in vitro, where 11 genes were novel. Of the latter JARID2 stood out as being necessary for formation of healthy fat cell metabolic phenotype by regulating expression of multiple fat-cell phenotype-specific genes. Conclusions This comprehensive RNAi screening in hASC suggests that a large proportion of WAT TFs that are impacted by metabolic conditions might be important for hyperplastic adipose tissue expansion. The screen also identified JARID2 as a novel TF essential for the development of functional adipocytes.

scholarly journals Clearing-factor lipase in adipose tissue. Distinction of different states of the enzyme and the possible role of the fat cell in the maintenance of tissue activity

1969 ◽  
Vol 112 (2) ◽  
pp. 203-209 ◽  
Author(s):  
V. J. Cunningham ◽  
D S Robinson
Keyword(s):  
Adipose Tissue ◽  
Lipase Activity ◽  
Total Activity ◽  
Epididymal Adipose Tissue ◽  
Fat Cells ◽  
Isolated Fat Cells ◽  
Fat Cell ◽  
Prolonged Incubation ◽  
Intact Tissue

1. Incubation of intact epididymal adipose tissue from fed rats at 37° in an albumin solution at pH7·4 in vitro results in rapid loss of clearing-factor lipase activity until a low activity, stable to prolonged incubation, is attained. The clearing-factor lipase activity of intact tissue from starved rats, which is initially much less than that of tissue from fed rats, is mainly stable to incubation at 37°. 2. Much of the clearing-factor lipase activity of intact epididymal adipose tissue from fed rats is inactivated by collagenase. The enzyme activity of intact tissue from starved rats is not inactivated by collagenase. 3. The clearing-factor lipase activity of fat cells isolated from the epididymal adipose tissue of fed rats is stable to prolonged incubation at 37°. It represents only a small proportion of the total activity of the intact tissue. In starved rats, the isolated fat cells contain a much higher proportion of the activity of the intact tissue. Their activity is also stable at 37°. 4. Incubation of isolated fat cells in a serum-based medium leads to a progressive rise in clearing-factor lipase activity. Actinomycin increases the extent of this rise in activity. No rise in clearing-factor lipase activity occurs when stromal-vascular cells isolated from epididymal adipose tissue are incubated in the medium. 5. The findings indicate that less than 20% of the activity of intact adipose tissue from fed rats is retained when fat cells are isolated from the tissue by collagenase treatment. The activity that is lost could be that which normally functions in the uptake of triglyceride fatty acids by the tissue.

Water content of rat adipose tissue and isolated adipocytes in relation to cell size

1976 ◽  
Vol 231 (5) ◽  
pp. 1568-1572 ◽  
Author(s):  
M DiGirolamo ◽  
JL Owens
Keyword(s):  
Adipose Tissue ◽  
Water Content ◽  
Cell Volume ◽  
Cell Size ◽  
Intracellular Water ◽  
Male Rats ◽  
Fat Cells ◽  
Fat Cell ◽  
Tissue Water ◽  
Adipose Mass

Epididymal adipose tissue composition and adipocyte water content were studied in male rats during growth and development of spontaneous obesity. The data show that a highly significant positive correlation exists between fat-cell volume and intracellular water space (IWS) (r=.967, P less than .001). Intracellular water, expressed as picoliters per fat cell, varied from 1.5-2 in small fat cells (mean vol, 30-50 pl) to 9-10 in large cells (800-1,000 pl). When expressed as percent of fat-cell volume, IWS varied from 5-7% in the small fat cells to 1-1.3% in the large ones. Total adipose tissue water continued to increase with increasing adipose mass. Similarly, total adipocyte water increased with enlarging cell size and tissue mass. The contribution of total adipocyte water (as contrasted to that of nonadipocyte water) to total tissue water, however, was found to be limited (less than 23%) and to decline progressively with adipose mass expansion.

Neonatal IL-4 exposure decreases adipogenesis of male rats into adulthood

2021 ◽  
Author(s):  
Tammy Ying ◽  
Thea N. Golden ◽  
Lan Cheng ◽  
Jeff Ishibashi ◽  
Patrick Seale ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Neonatal Period ◽  
Uncoupling Protein ◽  
Adipogenic Differentiation ◽  
Male Rats ◽  
Interleukin 4 ◽  
Sprague Dawley ◽  
Fat Cell ◽  
Subcutaneous White Adipose Tissue

The cytokine interleukin 4 (IL-4) can increase beige adipogenesis in adult rodents. However, neonatal animals use a distinct adipocyte precursor compartment for adipogenesis compared to adults. In this study, we address whether IL-4 can induce persistent effects on adipose tissue when administered subcutaneously in the interscapular region during the neonatal period in Sprague Dawley rats. We injected IL-4 into neonatal male rats during postnatal days 1-6, followed by analysis of adipose tissue and adipocyte precursors at 2 weeks and 10 weeks of age. Adipocyte precursors were cultured and subjected to differentiation in vitro. We found that a short and transient IL-4 exposure in neonates upregulated uncoupling protein 1 (Ucp1) mRNA expression and decreased fat cell size in subcutaneous white adipose tissue (WAT). Adipocyte precursors from mature rats that had been treated with IL-4 as neonates displayed a decrease in adiponectin (Adipoq) but no change in Ucp1 expression, as compared to controls. Thus, neonatal IL-4 induces acute beige adipogenesis and decreases adipogenic differentiation capacity long term. Overall, these findings indicate that the neonatal period is critical for adipocyte development and may influence the later onset of obesity.

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

2010 ◽  
Vol 2010 ◽  
pp. 1-20 ◽  
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.

Androgen regulation and site specificity of angiotensinogen gene expression and secretion in rat adipocytes

2000 ◽  
Vol 279 (6) ◽  
pp. E1398-E1405 ◽  
Author(s):  
Valérie Serazin-Leroy ◽  
Mireille Morot ◽  
Philippe de Mazancourt ◽  
Yves Giudicelli
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Mrna Expression ◽  
Protein Secretion ◽  
Male Rats ◽  
Fat Cells ◽  
Intact Male ◽  
Rat Adipocytes ◽  
Fat Deposits

Adipose tissue is an important source of angiotensinogen (ATG), and hypertension is commonly associated with android obesity. Therefore, we tested the hypothesis that androgens may control ATG gene expression and secretion in rat fat cells. In intact male rats, ATG mRNA expression (Northern blot and co-reverse transcription-polymerase chain reaction analysis) and protein secretion were significantly higher in deep intra-abdominal (perirenal and epididymal) than in subcutaneous adipocytes. After castration, ATG mRNA was reduced almost 50% in the three fat deposits, with parallel changes in ATG protein secretion. Conversely, testosterone treatment fully restored the ATG mRNA decrease after castration, whatever the anatomical origin of the adipocytes. Finally, a 24-h in vitro exposure of perirenal fat cells or differentiated preadipocytes from castrated rats to testosterone or dihydrotestosterone (10 nM free hormone concentration) increased ATG mRNA expression by 50–100%, an effect that was prevented by the anti-androgen cyproterone acetate. These data, demonstrating both in vivo and in vitro androgen induction of ATG mRNA expression in rat adipocytes, add further weight to the hypothesis of a link between adipose tissue ATG production, androgens, and android obesity-related hypertension.

scholarly journals Methionine requirement of kittens given amino acid diets containing adequate cystine

1983 ◽  
Vol 49 (3) ◽  
pp. 411-417 ◽  
Author(s):  
Katherine A. Smalley ◽  
Quinton R. Rogers ◽  
James G. Morris
Keyword(s):  
Adipose Tissue ◽  
Cell Size ◽  
Muscle Tissue ◽  
Dna Content ◽  
Shoulder Joint ◽  
Subcutaneous Adipose Tissue ◽  
Fat Cells ◽  
Fat Cell ◽  
Fat Cell Size ◽  
Subcutaneous Adipose

1. The effects of feeding either high-protein (HP) or low-protein (LP) diets between 1.8 and 15 kg live weight (LW) and a low-energy (LE) or high-energy (HE) intake subsequently on the cellularity of muscle and adipose tissue in pigs growing to 75 kg LW were investigated.2. The effects of the nutritional treatments on muscle tissue were assessed from the weight and DNA content of the m. adductor. For adipose tissue the total DNA content and fat cell size of the subcutaneous adipose tissue contained in the left shoulder joint were determined.3. Feeding the LP diets in early life reduced the weight and DNA content of the m. adductor (P < 0.01) and increased fat cell size (P < 0.01) at 15 kg LW.4. Subsequent to 15 kg there was an almost linear increase in muscle DNA with increasing LW, and the difference between pigs from the initial protein treatments progressively diminished and was no longer apparent at 60 kg LW.5. At 30 kg LW, pigs given the LP diets before 15 kg LW contained less DNA in the subcutaneous adipose tissue from the shoulder joint (P < 0.01) and had larger fat cells (P < 0.05) than pigs given the HP diets initially. However, adipose DNA and fat cell size increased with increasing LW and the differences resulting from the initial protein treatments progressively diminished. On the LE and HE treatments subsequent to 15 kg these differences were no longer evident at 45 and 60 kg respectively.6. Pigs given the HE intake subsequent to 15 kg, contained less DNA in muscle tissue (P < 0·05) at 60 and 75 kg LW and had larger fat cells (P < 0·05) at 45, 60 and 75 kg LW, than pigs on the LE treatment.

LIPOLYSIS IN CHICKEN ADIPOSE TISSUE IN VITRO

1969 ◽  
Vol 43 (2) ◽  
pp. 285-294 ◽  
Author(s):  
D. R. LANGSLOW ◽  
C. N. HALES
Keyword(s):  
Growth Hormone ◽  
Adipose Tissue ◽  
Sodium Succinate ◽  
Fat Cells ◽  
Propranolol Hydrochloride ◽  
Isolated Fat Cells ◽  
Adipose Tissue In Vitro ◽  
High Concentrations ◽  
Long Acting

SUMMARY The effects on lipolysis of various compounds have been studied in intact chicken adipose tissue and in isolated fat cells prepared from chicken adipose tissue. Glucagon stimulated lipolysis at concentrations down to 1 ng./ml. in intact pieces and 0·1 ng./ml. in isolated fat cells. The effect was enhanced by high concentrations of insulin. No anti-lipolytic effect of insulin was observed. Adrenaline, noradrenaline, porcine corticotrophin (ACTH) and long-acting ACTH were lipolytic but the effects were small and high concentrations were required. The adrenaline effect was blocked by propranolol hydrochloride. Dibutyryl 3′,5′-(cyclic)-AMP and theophylline stimulated lipolysis as did a combination of crude chicken growth hormone and hydrocortisone sodium succinate. It was concluded that the pattern of response of chicken adipose tissue was markedly different from that of the rat.

scholarly journals Fish Oil-induced Yellow Fat Disease in Rats; II. Enzyme Histochemistry of Adipose Tissue

1978 ◽  
Vol 15 (1) ◽  
pp. 125-132 ◽  
Author(s):  
L. H. J. C. Danse ◽  
W. A. Steenbergen-Botterweg
Keyword(s):  
Adipose Tissue ◽  
Acid Phosphatase ◽  
Fish Oil ◽  
Esterase Activity ◽  
Membrane Damage ◽  
Nonspecific Esterase ◽  
Fat Cells ◽  
Nucleotidase Activity ◽  
Fat Cell ◽  
Cell Degeneration

Adipose tissue in various stages of fish oil-induced yellow fat disease in the rat had the same acid phosphatase and 5-nucleotidase activity pattern as similar stages of the disorder in mink and pig. A weak acid phosphatase and 5-nucleotidase activity was seen in interstitial lipofuscin-laden macrophages in “stage M” yellow fat disease without fat cell degeneration. Activity of these macrophagic enzymes increased when there was fat cell degeneration (“stage S” and “stage E” yellow fat disease). This different phosphatase activity in the same cell type may result from phagocytosis of substrates with variable digestibility. Macrophages directly surrounding affected fat cells in steatitis areas (“stage S” and “stage E”) had strong acid phosphatase and 5-nucleotidase activity. As in the pig, increased 5-nucleotidase activity was found in affected fat cells, which probably indicates plasma membrane damage. Increased nonspecific esterase activity occurred around affected fat cells. Only a small part of this esterase activity originated from inflammatory cells. This indicates that an increase of esterase activity in degenerating adipose tissue may be an endogeneous process in this tissue.

Esterification of free fatty acids in adipocytes: a comparison between octanoate and oleate

2000 ◽  
Vol 349 (2) ◽  
pp. 463-471 ◽  
Author(s):  
Wen GUO ◽  
Ji-Kyung CHOI ◽  
James L. KIRKLAND ◽  
Barbara E. CORKEY ◽  
James A. HAMILTON
Keyword(s):  
Fatty Acids ◽  
Coconut Oil ◽  
Cell Number ◽  
Fat Cells ◽  
Fat Cell ◽  
Preadipocyte Differentiation ◽  
Undifferentiated Cells ◽  
Special Diets

Medium-chain triacylglycerols (MCT) are present in milk, coconut oil and other foods, and are used therapeutically in special diets for certain disorders of lipid and glucose utilization. Recently, it has become apparent that MCT are not only oxidized in the liver, but are also present in lymph and fat tissue, particularly after chronic treatment. To evaluate the influence of MCT on metabolism in fat cells, we compared incorporation of octanoate and oleate into cellular triacylglycerols of 3T3-L1 adipocytes as well as their effects on preadipocyte differentiation. We found that less octanoate than oleate was stored and that more octanoate than oleate was oxidized. Octanoate was esterified to a greater extent at the sn-1,3 position of glyceryl carbons than at the sn-2 position, whereas the opposite was true for oleate. Glycerol release from fat cells pre-treated with octanoate was also greater than from cells pre-treated with oleate, presumably related to the preferential release of octanoate from the sn-1,3 position. Octanoate was not incorporated into lipids in undifferentiated cells and did not induce differentiation in these cells, whereas oleate was readily stored and actually induced differentiation. Incorporation of octanoate into lipids increased as cells differentiated, but reached a maximum of about 10% of the total stored fatty acids. If these effects in vitro also occur in vivo, substitution of octanoate for oleate or other long-chain fatty acids could have the beneficial effect of diminishing fat-cell number and lipid content.

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