scholarly journals Degradation of insulin in vitro by liver and epididymal adipose tissue from obese–hyperglycaemic mice

1968 ◽  
Vol 106 (2) ◽  
pp. 543-547 ◽  
Author(s):  
Sighild Westman
Keyword(s):  
Adipose Tissue ◽  
Degradation Products ◽  
Serum Insulin ◽  
Epididymal Adipose Tissue ◽  
Insulin Degradation ◽  
Fat Depots ◽  
Insulin Tolerance ◽  
Tissue Homogenates ◽  
Assay Conditions

The insulin-degrading activity of liver supernatants and epididymal adipose-tissue homogenates from genetically obese–hyperglycaemic mice (ob ob) and their lean litter mates was studied by measurement of radioactive trichloroacetic acid-soluble degradation products of the insulin molecule. Optimum assay conditions for the decomposition of the hormone were devised. The properties of the degrading activity suggested the presence of enzymic insulin destruction in both the liver and epididymal adipose tissue. There was no difference in insulin degradation in liver samples from obese and lean mice when the results were related to the protein content of the supernatants. The epididymal adipose-tissue homogenates from obese mice displayed about eightfold higher degrading activity per unit of protein than did homogenates from lean animals. The physiological significance of this finding is discussed in the light of the increased fat depots, hyperphagia, raised serum insulin concentrations and increased insulin tolerance previously recorded in this strain of mice.

THE EFFECT OF FASTING ON THE ESTERIFICATION OF PALMITATE BY RAT EPIDIDYMAL ADIPOSE TISSUE IN VITRO

1967 ◽  
Vol 45 (6) ◽  
pp. 965-972 ◽  
Author(s):  
Anna M. Daniel ◽  
David Rubinstein
Keyword(s):  
Adipose Tissue ◽  
Neutral Lipids ◽  
Epididymal Adipose Tissue ◽  
Free Glycerol ◽  
Adipose Tissue In Vitro ◽  
Glucose Incorporation ◽  
Tissue Homogenates ◽  
Hydrolysis Of ◽  
Fat Pads

The effect of 48-h fasting on the in vitro esterification of fatty acids by rat epididymal adipose tissue was investigated. Fat pads from fed and fasted animals were incubated with palmitate-9,10-3H and glucose-U-14C. Fasting diminished the incorporation of both isotopes into glycerides. The decrease in glucose incorporation after fasting was found both in the glycerol and fatty acid moieties. The effect of fasting was not altered by the presence of insulin. Since lipotysis, which is increased after fasting, results in the preferential hydrolysis of newly synthesized triglycerides, the amount of labeled free glycerol after incubation was determined. It was insufficient to account for the decrease in glucose incorporation into lipids following fasting. The decrease in esterification of palmitate-9,10-3H could also be detected in free adipocytes and fat-free homogenates, but to a less extent than in intact tissue. Esterification by adipose-tissue homogenates from fasted animals was diminished in spite of optimum concentrations of substrates and coenzymes. The decrease in esterification was reflected in both neutral lipids and phosphatidic acid.

Cold effects in rat: plasma and adipose tissue free fatty acids and adipose lipase

1963 ◽  
Vol 204 (1) ◽  
pp. 157-164 ◽  
Author(s):  
Samuel Mallov
Keyword(s):  
Adipose Tissue ◽  
Lipolytic Activity ◽  
Rat Plasma ◽  
Epididymal Adipose Tissue ◽  
Albino Rats ◽  
Adipose Tissues ◽  
Tissue Sections ◽  
Tissue Homogenates ◽  
Increased Activity

Male albino rats were exposed to cold or kept at room temperature for 1–24 hr. Plasmas and epididymal adipose tissues were analyzed for free fatty acid (FFA) concentrations and lipolytic activities of intact sections and homogenates, as well as release of FFA by adipose tissues, determined in vitro. Plasmas of rats exposed to cold had significantly higher FFA levels than did plasmas from controls, and intact epididymal adipose tissue sections from cold-exposed rats had higher FFA concentrations, released greater quantities of FFA, and manifested higher lipase activities in the presence of activated triglyceride substrate than did sections from control rats. Exposure to cold may increase FFA mobilization from adipose tissues as a result of enhanced lipolytic activity, due to lipase activation by catecholamines released from adrenals and sympathetic nerve endings. The enzyme activated did not possess several of the properties characteristic of lipoprotein lipase. Tissue homogenates did not manifest increased activity after cold exposure, possibly as a result of activation by the homogenization process itself.

scholarly journals Histone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1210
Author(s):  
Amy K. Hauck ◽  
Tong Zhou ◽  
Ambuj Upadhyay ◽  
Yuxiang Sun ◽  
Michael B. O’Connor ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Disease ◽  
Adipose Tissue ◽  
Fat Depots ◽  
Michael Adducts ◽  
Lipid Aldehydes ◽  
Visceral Adipose ◽  
Fat Feeding

Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and specificity of this modification are largely unexplored. Here we show that histones are avidly modified by 4-hydroxynonenal (4-HNE) in vitro and in vivo. Carbonylation of histones by 4-HNE increased with age in male flies and visceral fat depots of mice and was potentiated in genetic (ob/ob) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from obese mice exclusively revealed Michael adducts. In total, we identified 11 sites of 4-hydroxy hexenal (4-HHE) and 10 sites of 4-HNE histone modification in visceral adipose tissue. In summary, these results characterize adipose histone carbonylation as a redox-linked epigenomic mark associated with metabolic disease and aging.

scholarly journals Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation

2018 ◽  
Vol 51 (3) ◽  
pp. 1051-1068 ◽  
Author(s):  
Jèssica Latorre ◽  
José M. Moreno-Navarrete ◽  
Mónica Sabater ◽  
Maria Buxo ◽  
José I. Rodriguez-Hermosa ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Low Grade ◽  
Metabolic Inflammation ◽  
Fat Depots ◽  
Acute Surgery ◽  
Obese Subjects ◽  
Anti Inflammatory ◽  
The Impact

Background/Aims: Obesity is characterized by the immune activation that eventually dampens insulin sensitivity and changes metabolism. This study explores the impact of different inflammatory/ anti-inflammatory paradigms on the expression of toll-like receptors (TLR) found in adipocyte cultures, adipose tissue, and blood. Methods: We evaluated by real time PCR the impact of acute surgery stress in vivo (adipose tissue) and macrophages (MCM) in vitro (adipocytes). Weight loss was chosen as an anti-inflammatory model, so TLR were analyzed in fat samples collected before and after bariatric surgery-induced weight loss. Associations with inflammatory and metabolic parameters were analyzed in non-obese and obese subjects, in parallel with gene expression measures taken in blood and isolated adipocytes/ stromal-vascular cells (SVC). Treatments with an agonist of TLR3 were conducted in human adipocyte cultures under normal conditions and upon conditions that simulated the chronic low-grade inflammatory state of obesity. Results: Surgery stress raised TLR1 and TLR8 in subcutaneous (SAT), and TLR2 in SAT and visceral (VAT) adipose tissue, while decreasing VAT TLR3 and TLR4. MCM led to increased TLR2 and diminished TLR3, TLR4, and TLR5 expressions in human adipocytes. The anti-inflammatory impact of weight loss was concomitant with decreased TLR1, TLR3, and TLR8 in SAT. Cross-sectional associations confirmed increased V/ SAT TLR1 and TLR8, and decreased TLR3 in obese patients, as compared with non-obese subjects. As expected, TLR were predominant in SVC and adipocyte precursor cells, even though expression of all of them but TLR8 (very low levels) was also found in ex vivo isolated and in vitro differentiated adipocytes. Among SVC, CD14+ macrophages showed increased TLR1, TLR2, and TLR7, but decreased TLR3 mRNA. The opposite patterns shown for TLR2 and TLR3 in V/ SAT, SVC, and inflamed adipocytes were observed in blood as well, being TLR3 more likely linked to lymphocyte instead of neutrophil counts. On the other hand, decreased TLR3 in adipocytes challenged with MCM dampened lipogenesis and the inflammatory response to Poly(I:C). Conclusion: Functional variations in the expression of TLR found in blood and hypertrophied fat depots, namely decreased TLR3 in lymphocytes and inflamed adipocytes, are linked to metabolic inflammation.

Abstract 128: Leptin: A Regulator of Aldosterone Synthase Expression & Aldosterone Secretion in Visceral Adipocytes, in Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Eric J Belin de Chantemele ◽  
Anne-Cecile Huby ◽  
P. T Menk ◽  
Weiqin Chen ◽  
Brian Lane ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cross Sections ◽  
Leptin Receptor ◽  
Zona Glomerulosa ◽  
Aldosterone Synthase ◽  
Leptin Receptors ◽  
Fat Depots ◽  
Physiological Relevance ◽  
Aldosterone Production

Obesity is associated with inappropriately high aldosterone levels, which contribute to the development of metabolic and cardiovascular disorders. The origin of these high aldosterone levels is incompletely understood. We recently demonstrated that the adipocyte-derived hormone leptin regulates aldosterone synthase (CYP11B2) expression and stimulates aldosterone release from adrenal zona glomerulosa cells. Recent studies demonstrate that adipocytes express CYP11B2 and secrete aldosterone. However, the mechanisms regulating aldosterone release from adipocytes remain unclear. Likewise, whether visceral (Visc) and subcutaneous (SubQ) adipose tissue contribute to a similar extent to aldosterone production is unknown. We tested the hypothesis that leptin increases adipocyte CYP11B2 expression and aldosterone production and investigated whether Visc and SubQ adipose tissues respond similarly to leptin. Immunostaining of mouse adipose tissue cross-sections and isolated mature adipocytes revealed that Visc and SubQ adipose tissue express leptin receptors. Treatment of mouse freshly isolated mature adipocytes, non-differenciated (stromal fraction) and differentiated adipocytes revealed that leptin dose-dependently increased CYP11B2 expression and aldosterone production in Visc adipose tissue only. Although leptin receptor and CYP11B2 levels were similar in SubQ and Visc adipocytes, SubQ adipocytes were unresponsive to leptin. The physiological relevance of these in vitro data was tested by measuring plasma aldosterone levels in mice deprived of adipose tissue (lipodystrophic mice) treated with leptin. Absence of adipose tissue in lipodystrophic mice blunted leptin-induced increases in aldosterone levels (WT-vehicle: 471±82 vs. WT-Leptin: 1699±396, p<0.05; KO-vehicle: 539±71 vs. KO+leptin: 787±156, NS). The human relevance of these data was determined by reporting that CYP11B2 expression gradually increased with body mass index in human mediastinal and omental fat depots. In summary these data strongly suggest that leptin regulates CYP11B2 levels and aldosterone release in visceral adipose tissue and that leptin-induced, adipocyte-derived aldosterone may contribute to obesity-associated hyperaldosteronism.

Metabolic influences on enzymes of glycogen synthesis and breakdown in adipose tissue

1964 ◽  
Vol 207 (6) ◽  
pp. 1215-1220 ◽  
Author(s):  
Alisa Gutman ◽  
Eleazar Shafrir
Keyword(s):  
Adipose Tissue ◽  
Protein Content ◽  
Glycogen Synthesis ◽  
Total Activity ◽  
Epididymal Adipose Tissue ◽  
Control Value ◽  
Prolonged Fast ◽  
Rat Adipose Tissue

Rat adipose tissue from different body sites was shown to contain uridine diphosphoglucose (UDPG)-transglucosylase activity, which on the basis of protein content was comparable to or higher than that reported for muscle or liver. In epididymal adipose tissue, the activity of UDPG-glycogen transglucosylase and phosphorylase, as well as the content of glycogen per wet weight, decreased with increasing age of the animals in parallel with the decrease of tissue protein content. On prolonged fast the activity of UDPG-glycogen transglucosylase and phosphorylase per milligram protein dropped by 25–50% of the control value. On refeeding, the extent of changes was variable but, in general, at 24 hr control or higher levels of activity were reached and at 48 hr the activities were elevated. The ratio of glucose 6-phosphate independent activity of UDPG-glycogen transglucosylase to total activity was not affected by fasting and refeeding or by the administration of glucose with insulin. In adrenalectomized rats, with high adipose tissue glycogen, no change in UDPG-glycogen transglucosylase was found, whereas the levels of phosphorylase were elevated. Epinephrine in vivo and in vitro did not affect the activity of UDPG-glycogen transglucosylase of adipose tissue.

Mechanism of enhanced lipolysis in adipose tissue of exercise-trained rats

1980 ◽  
Vol 239 (6) ◽  
pp. E422-E429 ◽  
Author(s):  
L. Bukowiecki ◽  
J. Lupien ◽  
N. Follea ◽  
A. Paradis ◽  
D. Richard ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Exercise Training ◽  
Food Restriction ◽  
Female Rats ◽  
Epididymal Adipose Tissue ◽  
Adipocyte Size ◽  
Fat Depots ◽  
Male And Female Rats ◽  
Receptor Sites ◽  
Stimulus Recognition

The effects of exercise training and food restriction on the regulation of lipolysis were studied comparatively in adipocytes isolated from male and female rats. Exercise training inhibited cell proliferation in parametrial, but not in epididymal adipose tissue, whereas it significantly reduced adipocyte size in both fat depots. Adipocyte capacity for responding lipolytically to epinephrine (10 microns) or to ACTH (1 micron) was markedly increased by exercise training. Enhanced lipolysis was also observed when cells isolated from exercise-trained animals were stimulated by bypassing with dibutyryl cyclic AMP (5 mM) or theophylline (5 mM) the early metabolic steps associated with hormonal activation of the adenylate cyclase complex. Significantly, binding of (-)-[3H]dihydroalprenolol to cellular receptor sites was not affected by exercise training. It is therefore concluded that exercise training increases adipocyte responsiveness to lipolytic hormones at a metabolic step distal to stimulus recognition by adrenoreceptors, possibly at the level of protein kinases or lipases. Food restriction markedly reduced adipocyte size and partially mimicked the effects of exercise training on adipocyte proliferation and lipolysis.

Factors Affecting the Inactivation of Insulin-125I by Rat Adipose Tissue

1971 ◽  
Vol 49 (5) ◽  
pp. 457-463 ◽  
Author(s):  
Alfred Fessler ◽  
Bernard Rubinstein ◽  
David Rubinstein ◽  
John C. Beck
Keyword(s):  
Adipose Tissue ◽  
Free Fraction ◽  
Tissue Homogenate ◽  
Immunoreactive Insulin ◽  
Insulin Degradation ◽  
Factors Affecting ◽  
Free Iodine ◽  
Tissue Homogenates ◽  
Rat Adipose Tissue ◽  
Tissue Fraction

The degradation of insulin-125I by adipose tissue was determined by the appearance of 125I in the trichloroacetic acid (TCA) soluble tissue fraction. A maximum of 30% of the 125I appears as TCA-soluble material following incubation with adipose tissue homogenates. Destruction of immunoreactive insulin and insulin-like activities is, however, complete. The appearance of TCA-soluble 125I is due to proteolysis rather than to deiodination since it can be decreased by the addition of unlabelled insulin to the incubation mixture. No increase in free iodine could be detected. The degradation of insulin by intact adipose tissue is greater than by free adipocytes. Tissue homogenization greatly increases the rate of insulin degradation. Most of the insulin-degrading activity is found in the "fat-free" fraction of the tissue homogenate, but this activity is rapidly lost during incubation at 37 °C. In contrast the lesser activity in the fat layer remains stable at 37°. N-Ethylmaleimide, which inhibits breakdown of the hormone by homogenates, increases the degradation of insulin by adipocytes. These results indicate that caution must be employed in interpreting binding and destruction of iodinated insulin and raise the possibility that insulin may penetrate the cell prior to its destruction.

FREE FATTY ACID METABOLISM IN CHINESE HAMSTERS

1966 ◽  
Vol 44 (1) ◽  
pp. 47-57 ◽  
Author(s):  
James Campbell ◽  
G. R. Green
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Spontaneous Diabetes ◽  
Chinese Hamster ◽  
Diabetic Rats ◽  
Epididymal Adipose Tissue ◽  
Time Interval ◽  
Adipose Tissues ◽  
Chinese Hamsters

In normal Chinese hamsters (Cricetulus griseus) the mean concentration of free fatty acids (FFA) in serum varied from group to group, but was (i) consistently 4 to 9 times greater than in rats, dogs, or man; (ii) slightly higher than in Syrian hamsters; (iii) two- to four-fold higher than in fasting or alloxan-diabetic rats. The epididymal adipose tissue of the Chinese hamster (i) had initial concentrations of FFA comparable to those in the rat and Syrian hamster; (ii) released, in the same time interval, 8- to 10-fold more FFA in vitro than this tissue of the rat; (iii) had higher concentrations of FFA after incubation than the incubated tissue of the rat. The retroperitoneal (perirenal) adipose tissue of the Chinese hamster was less active in release of fatty acids in vitro than the epididymal, but was, however, more active than the epididymal adipose tissue of the rat. These characteristics of FFA metabolism in the Chinese hamster were apparently attributable to species, not to age, diet, or sex. In the Chinese hamster, the weight of the epididymal adipose tissue per gram of body was relatively high. It appears that in this species the rate of release of fatty acids from adipose tissue is great, leading to high FFA concentrations in serum.In Chinese hamster and rat adipose tissues in vitro, glucose and insulin (separately) reduced the rate of release of FFA and the amount of FFA in the tissues, but glucose and insulin together produced the greatest reductions. The net reduction in FFA release by glucose and insulin in vitro was greater in tissue from the Chinese hamster. Insulin markedly increased glucose uptake by the adipose tissues of both species. The possible relation of the results to spontaneous diabetes in the Chinese hamster is discussed.

Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action

2006 ◽  
Vol 290 (6) ◽  
pp. E1253-E1261 ◽  
Author(s):  
Rong-Ze Yang ◽  
Mi-Jeong Lee ◽  
Hong Hu ◽  
Jessica Pray ◽  
Hai-Bin Wu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cdna Library ◽  
Insulin Action ◽  
Signal Sequence ◽  
Visceral Obesity ◽  
Northern Analysis ◽  
Protein Sequence Analysis ◽  
Omental Adipose Tissue ◽  
Fat Depots

Central (visceral) obesity is more closely associated with insulin resistance, type 2 diabetes, and cardiovascular disease than is peripheral [subcutaneous (sc)] obesity, but the underlying mechanism for this pathophysiological difference is largely unknown. To understand the molecular basis of this difference, we sequenced 10,437 expressed sequence tags (ESTs) from a human omental fat cDNA library and discovered a novel visceral fat depot-specific secretory protein, which we have named omentin. Omentin ESTs were more abundant than many known adipose genes, such as perilipin, adiponectin, and leptin in the cDNA library. Protein sequence analysis indicated that omentin mRNA encodes a peptide of 313 amino acids, containing a secretory signal sequence and a fibrinogen-related domain. Northern analysis demonstrated that omentin mRNA was predominantly expressed in visceral adipose tissue and was barely detectable in sc fat depots in humans and rhesus monkeys. Quantative real-time PCR showed that omentin mRNA was expressed in stromal vascular cells, but not fat cells, isolated from omental adipose tissue, with >150-fold less in sc cell fractions. Accordingly, omentin protein was secreted into the culture medium of omental, but not sc, fat explants. Omentin was detectable in human serum by Western blot analysis. Addition of recombinant omentin in vitro did not affect basal but enhanced insulin-stimulated glucose uptake in both sc (47%, n = 9, P = 0.003) and omental (∼30%, n = 3, P < 0.05) human adipocytes. Omentin increased Akt phosphorylation in the absence and presence of insulin. In conclusion, omentin is a new adipokine that is expressed in omental adipose tissue in humans and may regulate insulin action.

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