File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1007/s00125-007-0809-7
- PMID: 17710465
- Find via
Supplementary
-
Citations:
- PubMed Central: 0
- Appears in Collections:
Conference Paper: Macrophage-adipocyte cross-talk in the initiation of obesity-related insulin resistance and type 2 diabetes: role of adiponectin
Title | Macrophage-adipocyte cross-talk in the initiation of obesity-related insulin resistance and type 2 diabetes: role of adiponectin |
---|---|
Authors | |
Issue Date | 2007 |
Publisher | Berlin Springer Verlag |
Citation | The 43rd Annual Meeting of the European Association of the Study of Diabetes (EASD), Amsterdam, The Netherlands, 17-21 September 2007. In Diabetologia, 2007, v. 50 n. S1, p. S69-S70 How to Cite? |
Abstract | Background and Aims: Recent studies suggest that, in obesity, chronic
inflammation of adipose tissues (AT) with macrophage infiltration and enhanced expression of pro-inflammatory cytokines plays a significant role
in the development of obesity-related metabolic disorders, such as type
2 diabetes. We have previously demonstrated that adenovirus-mediated
over-expression of adiponectin, an insulin-sensitizing adipokine with antiinflammatory
action and reduced expression in obesity, results in a marked
down-regulation of several inflammation-related genes, including F4/80 (a
macrophage marker) and monocyte chemotactic protein-1 (MCP-1), in the
white AT of db/db diabetic mice (Lam & Xu, Curr Diab Rep 2005;5:254-9).
As MCP-1 has been suggested to contribute to macrophage infiltration of AT
in db/db mice (Kanda et al, JCI 2006;116:1494-505), we hypothesize that the
reduced expression of adiponectin in obesity may play an important role in
initiating the macrophage-adipocyte cross-talk which leads to obesity-related
insulin resistance and diabetes. This study aims at determining the time course
and magnitude of macrophage infiltration and inflammatory activation in
AT, in relation to changes in the AT levels of adiponectin, glucose tolerance
and insulin sensitivity, in db/db diabetic mice.
Materials and Methods: At the age of 5, 6, 7, 8, 9, 10, 11, 12 weeks, male db/
db mice and lean controls were tested for blood glucose (non-fasting, fasting,
and in response to ip. insulin tolerance test and glucose tolerance test), insulin
and lipid levels. The mRNA expression level of adiponectin, MCP-1 and F4/80
were determined by real-time PCR in epididymal fat pads obtained after
sacrifice of mice at different ages. Immunohistochemistry was performed to
assess the severity of macrophage infiltration in AT. Adiponectin and MCP-1
were also measured by ELISA in medium obtained after the fat pads were
incubated for 24 hours.
Results: Compared to lean controls, db/db mice had significant increases
in the weight of AT in 3 depots (epididymal, perirenal and abdominal
subcutaneous) at 5 weeks, accompanied by significant hyperinsulinaemia
and hypercholesterolaemia, and a trend towards impaired responses during
insulin tolerance test, compared to lean controls. A significant 80% reduction
in adipose tissue adiponectin mRNA expression, accompanied by significant
reductions in adiponectin in the explant mediium, was also seen at 5 weeks,
when no significant increase was found in F4/80 mRNA expression or
macrophage infiltration of epididymal AT. There was also no significant
increase in the release of MCP-1 during AT explant incubation at 5 weeks.
Greater weight than controls, accompanied by impaired glucose tolerance,
was seen from 6 weeks. Non-fasting hyperglycaemia, compared to lean
controls, became evident at 8 weeks. By 10 weeks, fasting hyperglycaemia
was established.
Conclusion: These data suggest that reduced adiponectin expression precedes
the macrophage infiltration in AT of db/db mice and may contribute, at least
in part, to the macrophage infiltration and inflammatory gene activation
in white AT in obese animals. Hyperinsulinaemia precedes macrophage
infiltration of AT which may, nevertheless, contribute to progressive insulin
resistance and development of diabetes in the db/db mice.
Supported by RGC grant. |
Persistent Identifier | http://hdl.handle.net/10722/102243 |
ISSN | 2023 Impact Factor: 8.4 2023 SCImago Journal Rankings: 3.355 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lau, TYI | en_HK |
dc.contributor.author | Ye, HY | en_HK |
dc.contributor.author | Xu, A | en_HK |
dc.contributor.author | Lam, KSL | en_HK |
dc.date.accessioned | 2010-09-25T20:22:48Z | - |
dc.date.available | 2010-09-25T20:22:48Z | - |
dc.date.issued | 2007 | en_HK |
dc.identifier.citation | The 43rd Annual Meeting of the European Association of the Study of Diabetes (EASD), Amsterdam, The Netherlands, 17-21 September 2007. In Diabetologia, 2007, v. 50 n. S1, p. S69-S70 | - |
dc.identifier.issn | 0012-186X | - |
dc.identifier.uri | http://hdl.handle.net/10722/102243 | - |
dc.description.abstract | Background and Aims: Recent studies suggest that, in obesity, chronic inflammation of adipose tissues (AT) with macrophage infiltration and enhanced expression of pro-inflammatory cytokines plays a significant role in the development of obesity-related metabolic disorders, such as type 2 diabetes. We have previously demonstrated that adenovirus-mediated over-expression of adiponectin, an insulin-sensitizing adipokine with antiinflammatory action and reduced expression in obesity, results in a marked down-regulation of several inflammation-related genes, including F4/80 (a macrophage marker) and monocyte chemotactic protein-1 (MCP-1), in the white AT of db/db diabetic mice (Lam & Xu, Curr Diab Rep 2005;5:254-9). As MCP-1 has been suggested to contribute to macrophage infiltration of AT in db/db mice (Kanda et al, JCI 2006;116:1494-505), we hypothesize that the reduced expression of adiponectin in obesity may play an important role in initiating the macrophage-adipocyte cross-talk which leads to obesity-related insulin resistance and diabetes. This study aims at determining the time course and magnitude of macrophage infiltration and inflammatory activation in AT, in relation to changes in the AT levels of adiponectin, glucose tolerance and insulin sensitivity, in db/db diabetic mice. Materials and Methods: At the age of 5, 6, 7, 8, 9, 10, 11, 12 weeks, male db/ db mice and lean controls were tested for blood glucose (non-fasting, fasting, and in response to ip. insulin tolerance test and glucose tolerance test), insulin and lipid levels. The mRNA expression level of adiponectin, MCP-1 and F4/80 were determined by real-time PCR in epididymal fat pads obtained after sacrifice of mice at different ages. Immunohistochemistry was performed to assess the severity of macrophage infiltration in AT. Adiponectin and MCP-1 were also measured by ELISA in medium obtained after the fat pads were incubated for 24 hours. Results: Compared to lean controls, db/db mice had significant increases in the weight of AT in 3 depots (epididymal, perirenal and abdominal subcutaneous) at 5 weeks, accompanied by significant hyperinsulinaemia and hypercholesterolaemia, and a trend towards impaired responses during insulin tolerance test, compared to lean controls. A significant 80% reduction in adipose tissue adiponectin mRNA expression, accompanied by significant reductions in adiponectin in the explant mediium, was also seen at 5 weeks, when no significant increase was found in F4/80 mRNA expression or macrophage infiltration of epididymal AT. There was also no significant increase in the release of MCP-1 during AT explant incubation at 5 weeks. Greater weight than controls, accompanied by impaired glucose tolerance, was seen from 6 weeks. Non-fasting hyperglycaemia, compared to lean controls, became evident at 8 weeks. By 10 weeks, fasting hyperglycaemia was established. Conclusion: These data suggest that reduced adiponectin expression precedes the macrophage infiltration in AT of db/db mice and may contribute, at least in part, to the macrophage infiltration and inflammatory gene activation in white AT in obese animals. Hyperinsulinaemia precedes macrophage infiltration of AT which may, nevertheless, contribute to progressive insulin resistance and development of diabetes in the db/db mice. Supported by RGC grant. | - |
dc.language | eng | en_HK |
dc.publisher | Berlin Springer Verlag | - |
dc.relation.ispartof | Diabetologia | en_HK |
dc.title | Macrophage-adipocyte cross-talk in the initiation of obesity-related insulin resistance and type 2 diabetes: role of adiponectin | en_HK |
dc.type | Conference_Paper | en_HK |
dc.identifier.email | Xu, A: amxu@hkucc.hku.hk | en_HK |
dc.identifier.email | Lam, KSL: ksllam@hku.hk | en_HK |
dc.identifier.authority | Xu, A=rp00485 | en_HK |
dc.identifier.authority | Lam, KSL=rp00343 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1007/s00125-007-0809-7 | - |
dc.identifier.pmid | 17710465 | - |
dc.identifier.hkuros | 137227 | en_HK |
dc.identifier.volume | 50 | - |
dc.identifier.issue | suppl. 1 | - |
dc.identifier.spage | S69 | - |
dc.identifier.epage | S70 | - |
dc.identifier.issnl | 0012-186X | - |