Site-specific differences in the action of NRTI drugs on adipose tissue incubated in vitro with lymphoid cells, and their interaction with dietary lipids

Author(s):  
Christine A. Mattacks ◽  
Dawn Sadler ◽  
Caroline M. Pond
2006 ◽  
Vol 191 (1) ◽  
pp. 101-111 ◽  
Author(s):  
David J Flint ◽  
Nadine Binart ◽  
Stephanie Boumard ◽  
John J Kopchick ◽  
Paul Kelly

Direct metabolic effects of GH on adipose tissue are well established, but effects of prolactin (PRL) have been more controversial. Recent studies have demonstrated PRL receptors on adipocytes and effects of PRL on adipose tissue in vitro. The role of GH in adipocyte proliferation and differentiation is also controversial, since GH stimulates adipocyte differentiation in cell lines, whereas it stimulates proliferation but inhibits differentiation of adipocytes in primary cell culture. Using female gene disrupted (ko) mice, we showed that absence of PRL receptors (PRLRko) impaired development of both internal and s.c. adipose tissue, due to reduced numbers of adipocytes, an effect differing from that of reduced food intake, where cell volume is decreased. In contrast, GHRko mice exhibited major decreases in the number of internal adipocytes, whereas s.c. adipocyte numbers were increased, even though body weight was decreased by 40–50%. The changes in adipose tissue in PRLRko mice appeared to be entirely due to extrinsic factors since preadipocytes proliferated and differentiated in similar fashion to wild-type animals in vitro and their response to insulin and isoproterenol was similar to wild-type animals. This contrasted with GHRko mice, where s.c. adipocytes proliferated, differentiated, and responded to hormones in identical fashion to controls, whereas parametrial adipocytes exhibited markedly depressed proliferation and differentiation potential and failed to respond to insulin or noradrenaline. Our results provide in vivo evidence that both GH and PRL stimulate differentiation of adipocytes but that the effects of GH are site specific and induce intrinsic changes in the precursor population, which are retained in vitro.


1997 ◽  
Vol 77 (4) ◽  
pp. 621-643 ◽  
Author(s):  
Christine A. Mattacks ◽  
Caroline M. Pond

The effects of diet on the composition and properties of adipose tissue in relation to lymph nodes were studied in adult guinea-pigs. The proportions of monoenoic triacylglycerol fatty acids were constant in all sites in adipose tissue of similarly fed guinea-pigs, but were substantially greater in samples from guinea-pigs fed on suet-enriched chow. Triacylglycerols in adipose tissue from near nodes contained significantly fewer saturated fatty acids, and significantly more 18:2n−6 and 18:3n−3 than those in samples from sites remote from nodes within the same depot. Depots that interact most strongly with lymphoid cellsin vitrohad the largest and most consistent within-depot differences. The gradients of triacylgiycerol fatty acid composition with distance from lymph nodes in two small intermuscular depots were similar in guinea-pigs fed on plain or suet-enriched chow. These findings are consistent with the hypothesis that adipose tissue around lymph nodes is specialized for local interactions with the lymphoid cells therein, and help to explain the variability of serial or duplicate measurements of adipose tissue composition. When cultured alone, lipopolysaccharide-stimulated lymph node lymphoid cells from suet-fed guinea-pigs incorporated as much labelled thymidine as the controls. Adipose tissue explants from suet-fed guinea-pigs inhibited lymphocyte proliferation much less than those of the controls, although the site-specific differences were similar. The pattern of site-specific differences in glycerol released from explants incubated alone was generally similar for both dietary groups, but except in the popliteal depot, the increases following co-culturing with lymphoid cells were smaller for samples from suet-fed guinea-pigs. These experiments show that minor changes in the fatty acid composition of the diet can substantially alter the interactions between adipose tissue and lymphoid cells.


2002 ◽  
Vol 87 (4) ◽  
pp. 375-382 ◽  
Author(s):  
Christine A. Mattacks ◽  
Dawn Sadler ◽  
Caroline M. Pond

The effects of feeding beef suet (mostly saturated and monoenoic fatty acids), sunflower oil (rich inn-6 fatty acids) and fish oil (rich inn-3 fatty acids) on the response of mesenteric, omental, popliteal and perirenal adipocytes to experimentally-induced local inflammation were studied in adult guinea pigs. After 6 weeks on the experimental diets, the animals were fed standard chow, and lipopolysaccharide was injected unilaterally daily for 4 d to induce swelling of one popliteal lymph node. Basal lipolysis in the perinodal adipocytes of all depots studied was higher in the sunflower oil-fed animals than in the controls fed on standard chow, and lower in those fed on suet or fish oil. Dietary lipids altered rates of lipolysis during incubation with 10-5M noradrenaline in all samples studied from the locally-activated popliteal depot, but only in adipocytes within 5 mm of a large lymph node in the other depots. The fish-oil diet attenuated the spread of increased lipolysis within the locally-activated popliteal adipose tissue, and from this depot to other node-containing depots. These experiments show thatn-6 polyunsaturated fatty acids promote andn-3 fatty acids suppress the spread of immune activation to adipocytes within and between depots, and alter the sensitivity of perinodal adipocytes to noradrenaline. Dietary effects are reduced or absent in adipocytes in sites remote from lymph nodes, and thus such samples do not adequately represent processes in perinodal adipose tissue. These results are consistent with the hypothesis that perinodal adipocytes interact with adjacent lymphoid cells during immune responses.


2008 ◽  
Vol 100 (4) ◽  
pp. 722-730 ◽  
Author(s):  
Anabelle Redonnet ◽  
Carine Ferrand ◽  
Céline Bairras ◽  
Paul Higueret ◽  
Catherine Noël-Suberville ◽  
...  

In order to study the effects of dietary lipids and vitamin A on the development of adipose tissues, young rats were submitted for 8 d to a control or to two cafeteria diets with normal (Caf) or higher (Caf+) vitamin A levels. Retinoid (retinoic acid receptor (RAR) α, RARγ, retinoid X receptor (RXR) α) and fatty acid (PPARγ) receptor mRNA was measured in the subcutaneous white adipose tissue (Swat) and in isolated mature adipocytes by RT-PCR. The stroma vascular fraction was cultured in vitro to test the capacities of the adipocyte precursors to proliferate and differentiate. The Caf diet enriched in vitamin A resulted in an increased adiposity, due to increased adipocyte hypertrophy. This was concomitant with a lower expression of RARα and RARγ mRNA ( − 34·6 and − 38·6 %) and a higher expression of PPARγ (+59 %) in the Swat and, to a less extent, in isolated adipocytes. Positive correlations were obtained between PPARγ mRNA and Swat weights and between PPARγ and RXRα mRNA. By contrast, RARγ mRNA and Swat masses were negatively correlated. The adipocyte precursors from Caf+ Swat proliferated more, in vitro, at the beginning of the culture. This difference progressively disappeared and was totally absent after 8 d of culture, but with a higher percentage of differentiated preadipocytes (+80·3 %) in the Caf+ group. In conclusion, lipids and vitamin A act synergistically on the normal growth of the adipose tissue in young rats, concomitant with an imbalance in the pattern of the nuclear receptors. These changes influence the early normal development of the endogenous adipocyte precursors.


1975 ◽  
Vol 33 (2) ◽  
pp. 291-297 ◽  
Author(s):  
P. W. Larking ◽  
E. R. Nye

1. Rats were fed for 8 weeks on one of five diets differing in the amount of fatty acids 18:1, 18:2 and 18:3. Lipolysis, in vitro, of epididymal fat from fed and fasted rats was measured both basally and in the presence of noradrenaline with and without prostaglandin E12. Lipolysis was markedly influenced by the type of dietary fat. In particular, lipolysis in adipose tissue from rats given diets rich in the fatty acid 18:3 was higher than in the rats given diets containing 18:23. Results showing the effects of fasting on adipose tissue lipolysis are also presented4. The results are discussed in relation to the known effects of unsaturated fats on hyper-plasia and protein synthesis in adipose tissue and on the possible role of prostaglandins.


1999 ◽  
Vol 24 ◽  
pp. 9-20 ◽  
Author(s):  
C. M. Pond ◽  
E. A. Newsholme

AbstractEthological and ecological studies of wild animals are producing evidence for metabolic stress during courtship, breeding and parental care comparable with that of domestic livestock. Resistance to disease may be compromised by the demand for fatty acids and proteins during reproduction and even more during lactation. The adipose tissue around major lymph nodes is indistinguishable histologically from that in larger depots. In vitro and in vivo studies reveal that it is specialized to respond to lipolytic agonists secreted by lymphoid cells but is insensitive to the endocrine conditions of short-term fasting. These properties enable it to provision adjacent immune cells. Such adipose tissue may act as a forum for competing demands of mammary glands, muscles etc. and local defences against pathogens. Glutamine is essential to the nutrition of the immune system and is used by the mammary gland. Muscle is the best known source but adipose tissue also participates in glutamine metabolism and may become more important in animals in which the musculature is wasted through prolonged lactation.


1969 ◽  
Vol 61 (1_Suppl) ◽  
pp. S156
Author(s):  
Suad Efendić ◽  
Peter Amer ◽  
Jan Östman

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