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Tracing the movement of adiponectin in a parabiosis model of wild-type and adiponectin-knockout mice.

Nakatsuji H, Kishida K, Sekimoto R, Funahashi T, Shimomura I - FEBS Open Bio (2014)

Bottom Line: Hypoadiponectinemia is associated in obese individuals with insulin resistance and atherosclerosis.In the WT-KO parabiosis model, circulating adiponectin levels of the WT partners decreased rapidly, on the other hand, those of KO partners increased, and then these reached comparable levels each other at day 7.In the diet-induced obesity model, high adiponectin protein levels were detected in adipose stromal vascular fraction of diet-induced obese KO partner, without changes in its binding proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.

ABSTRACT
Adiponectin is exclusively synthesized by adipocytes and exhibits anti-diabetic, anti-atherosclerotic and anti-inflammatory properties. Hypoadiponectinemia is associated in obese individuals with insulin resistance and atherosclerosis. However, the mechanisms responsible for hypoadiponectinemia remain unclear. Here, we investigated adiponectin movement using hetero parabiosis model of wild type (WT) and adiponectin-deficient (KO) mice. WT mice were parabiosed with WT mice (WT-WT) or KO mice (WT-KO) and adiponectin levels were measured serially up to 63 days after surgery. In the WT-KO parabiosis model, circulating adiponectin levels of the WT partners decreased rapidly, on the other hand, those of KO partners increased, and then these reached comparable levels each other at day 7. Circulating adiponectin levels decreased further to the detection limit of assay, and remained low up to day 63. However, adiponectin protein was detected in the adipose tissues of not only the WT partner but also WT-KO mice. In the diet-induced obesity model, high adiponectin protein levels were detected in adipose stromal vascular fraction of diet-induced obese KO partner, without changes in its binding proteins. The use of parabiosis experiments shed light on movement of native adiponectin among different tissues such as the state of hypoadiponectinemia in obesity.

No MeSH data available.


Related in: MedlinePlus

Effect of parabiosis. (A) Experimental protocol. WT mice were parabiosed with WT mice (WT–WT) or adiponectin knockout mice (WT–KO). At 63 days after surgery, the mice were sacrificed and their tissues analyzed. WT; wild type mice, KO; adiponectin knockout mice. (B) Body weight of parabiosed mice. n.s.; not significant. (C) Plasma glucose, insulin and adiponectin levels were measured in partners of parabiosed mice. WT (WT–WT); WT mice of WT–WT pair, WT (WT–KO); WT mice of WT–KO pair, KO (WT–KO); KO mice of WT–KO pair. Data are mean ± SEM. Each experiment was repeated at least three times.
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f0005: Effect of parabiosis. (A) Experimental protocol. WT mice were parabiosed with WT mice (WT–WT) or adiponectin knockout mice (WT–KO). At 63 days after surgery, the mice were sacrificed and their tissues analyzed. WT; wild type mice, KO; adiponectin knockout mice. (B) Body weight of parabiosed mice. n.s.; not significant. (C) Plasma glucose, insulin and adiponectin levels were measured in partners of parabiosed mice. WT (WT–WT); WT mice of WT–WT pair, WT (WT–KO); WT mice of WT–KO pair, KO (WT–KO); KO mice of WT–KO pair. Data are mean ± SEM. Each experiment was repeated at least three times.

Mentions: To investigate the effects of long-term adiponectin recruitment in adipose tissues, WT mice were parabiosed with WT mice (WT–WT) or KO mice (WT–KO) (Fig. 1A). There was no significant difference in body weight of WT–WT and WT–KO pairs (Fig. 1B). Serial measurements of plasma glucose and insulin levels showed similar levels in WT partners of WT–WT [WT (WT–WT)], WT partners of WT–KO [WT (WT–KO)] and KO partners of WT–KO [KO (WT–KO)] (Fig. 1C). Serial measurements of circulating adiponectin levels by ELISA showed increased levels at day 14 in WT (WT–WT), followed by plateau at 15–18 μg/mL (Fig. 1C). This was in contrast to WT (WT–KO) parabiotic mice, which showed rapid fall in circulating adiponectin levels. On the other hand, the levels in KO (WT–KO) increased initially and then at day 7 reached levels comparable to those of WT (WT–KO) (Fig. 1C). Previous reports showed that cross-circulation was established by day 3 after parabiosis surgery [20,21]. Our results showed that adiponectin migrated from WT mice to KO mice through the bloodstream. Interestingly, since day 7, circulating adiponectin levels decreased markedly below the detection limit of ELISA assay, and remained at those low levels up to day 63 (Fig. 1C).


Tracing the movement of adiponectin in a parabiosis model of wild-type and adiponectin-knockout mice.

Nakatsuji H, Kishida K, Sekimoto R, Funahashi T, Shimomura I - FEBS Open Bio (2014)

Effect of parabiosis. (A) Experimental protocol. WT mice were parabiosed with WT mice (WT–WT) or adiponectin knockout mice (WT–KO). At 63 days after surgery, the mice were sacrificed and their tissues analyzed. WT; wild type mice, KO; adiponectin knockout mice. (B) Body weight of parabiosed mice. n.s.; not significant. (C) Plasma glucose, insulin and adiponectin levels were measured in partners of parabiosed mice. WT (WT–WT); WT mice of WT–WT pair, WT (WT–KO); WT mice of WT–KO pair, KO (WT–KO); KO mice of WT–KO pair. Data are mean ± SEM. Each experiment was repeated at least three times.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4048846&req=5

f0005: Effect of parabiosis. (A) Experimental protocol. WT mice were parabiosed with WT mice (WT–WT) or adiponectin knockout mice (WT–KO). At 63 days after surgery, the mice were sacrificed and their tissues analyzed. WT; wild type mice, KO; adiponectin knockout mice. (B) Body weight of parabiosed mice. n.s.; not significant. (C) Plasma glucose, insulin and adiponectin levels were measured in partners of parabiosed mice. WT (WT–WT); WT mice of WT–WT pair, WT (WT–KO); WT mice of WT–KO pair, KO (WT–KO); KO mice of WT–KO pair. Data are mean ± SEM. Each experiment was repeated at least three times.
Mentions: To investigate the effects of long-term adiponectin recruitment in adipose tissues, WT mice were parabiosed with WT mice (WT–WT) or KO mice (WT–KO) (Fig. 1A). There was no significant difference in body weight of WT–WT and WT–KO pairs (Fig. 1B). Serial measurements of plasma glucose and insulin levels showed similar levels in WT partners of WT–WT [WT (WT–WT)], WT partners of WT–KO [WT (WT–KO)] and KO partners of WT–KO [KO (WT–KO)] (Fig. 1C). Serial measurements of circulating adiponectin levels by ELISA showed increased levels at day 14 in WT (WT–WT), followed by plateau at 15–18 μg/mL (Fig. 1C). This was in contrast to WT (WT–KO) parabiotic mice, which showed rapid fall in circulating adiponectin levels. On the other hand, the levels in KO (WT–KO) increased initially and then at day 7 reached levels comparable to those of WT (WT–KO) (Fig. 1C). Previous reports showed that cross-circulation was established by day 3 after parabiosis surgery [20,21]. Our results showed that adiponectin migrated from WT mice to KO mice through the bloodstream. Interestingly, since day 7, circulating adiponectin levels decreased markedly below the detection limit of ELISA assay, and remained at those low levels up to day 63 (Fig. 1C).

Bottom Line: Hypoadiponectinemia is associated in obese individuals with insulin resistance and atherosclerosis.In the WT-KO parabiosis model, circulating adiponectin levels of the WT partners decreased rapidly, on the other hand, those of KO partners increased, and then these reached comparable levels each other at day 7.In the diet-induced obesity model, high adiponectin protein levels were detected in adipose stromal vascular fraction of diet-induced obese KO partner, without changes in its binding proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.

ABSTRACT
Adiponectin is exclusively synthesized by adipocytes and exhibits anti-diabetic, anti-atherosclerotic and anti-inflammatory properties. Hypoadiponectinemia is associated in obese individuals with insulin resistance and atherosclerosis. However, the mechanisms responsible for hypoadiponectinemia remain unclear. Here, we investigated adiponectin movement using hetero parabiosis model of wild type (WT) and adiponectin-deficient (KO) mice. WT mice were parabiosed with WT mice (WT-WT) or KO mice (WT-KO) and adiponectin levels were measured serially up to 63 days after surgery. In the WT-KO parabiosis model, circulating adiponectin levels of the WT partners decreased rapidly, on the other hand, those of KO partners increased, and then these reached comparable levels each other at day 7. Circulating adiponectin levels decreased further to the detection limit of assay, and remained low up to day 63. However, adiponectin protein was detected in the adipose tissues of not only the WT partner but also WT-KO mice. In the diet-induced obesity model, high adiponectin protein levels were detected in adipose stromal vascular fraction of diet-induced obese KO partner, without changes in its binding proteins. The use of parabiosis experiments shed light on movement of native adiponectin among different tissues such as the state of hypoadiponectinemia in obesity.

No MeSH data available.


Related in: MedlinePlus