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The portal theory supported by venous drainage-selective fat transplantation.

Rytka JM, Wueest S, Schoenle EJ, Konrad D - Diabetes (2010)

Bottom Line: In the present study, we used a fat transplantation paradigm to (artificially) increase intra-abdominal fat mass to test the hypothesis that venous drainage of fat tissue determines its impact on glucose homeostasis.Epididymal fat pads of C57Bl6/J donor mice were transplanted into littermates, either to the parietal peritoneum (caval/systemic venous drainage) or, by using a novel approach, to the mesenterium, which confers portal venous drainage.These results demonstrate that the metabolic fate of intra-abdominal fat tissue transplantation is determined by the delivery of inflammatory cytokines to the liver specifically via the portal system, providing direct evidence in support of the portal hypothesis.

View Article: PubMed Central - PubMed

Affiliation: University Children’s Hospital, Zurich, Switzerland.

ABSTRACT

Objective: The "portal hypothesis" proposes that the liver is directly exposed to free fatty acids and cytokines increasingly released from visceral fat tissue into the portal vein of obese subjects, thus rendering visceral fat accumulation particularly hazardous for the development of hepatic insulin resistance and type 2 diabetes. In the present study, we used a fat transplantation paradigm to (artificially) increase intra-abdominal fat mass to test the hypothesis that venous drainage of fat tissue determines its impact on glucose homeostasis.

Research design and methods: Epididymal fat pads of C57Bl6/J donor mice were transplanted into littermates, either to the parietal peritoneum (caval/systemic venous drainage) or, by using a novel approach, to the mesenterium, which confers portal venous drainage.

Results: Only mice receiving the portal drained fat transplant developed impaired glucose tolerance and hepatic insulin resistance. mRNA expression of proinflammatory cytokines was increased in both portally and systemically transplanted fat pads. However, portal vein (but not systemic) plasma levels of interleukin (IL)-6 were elevated only in mice receiving a portal fat transplant. Intriguingly, mice receiving portal drained transplants from IL-6 knockout mice showed normal glucose tolerance.

Conclusions: These results demonstrate that the metabolic fate of intra-abdominal fat tissue transplantation is determined by the delivery of inflammatory cytokines to the liver specifically via the portal system, providing direct evidence in support of the portal hypothesis.

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Related in: MedlinePlus

A: Left panel: Hematoxylin- and eosin-stained liver sections from sham-operated and pTx mice. Right panel: Total liver lipids were determined and expressed relative to liver weight. Results represent the mean ± SEM of four to six mice of each group. B: mRNA expression of indicated markers in liver tissue of sham-operated and pTx mice was analyzed. Results are the mean ± SEM of five mice per group, expressed relative to sham-operated mice and normalized to expression of 18S. C: FFA levels were determined in systemic and portal plasma samples of mice receiving a portal drained fat transplant (pTx) and in sham-operated mice after 3 h of fasting. Results are the mean ± SEM of five to six animals.
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Figure 4: A: Left panel: Hematoxylin- and eosin-stained liver sections from sham-operated and pTx mice. Right panel: Total liver lipids were determined and expressed relative to liver weight. Results represent the mean ± SEM of four to six mice of each group. B: mRNA expression of indicated markers in liver tissue of sham-operated and pTx mice was analyzed. Results are the mean ± SEM of five mice per group, expressed relative to sham-operated mice and normalized to expression of 18S. C: FFA levels were determined in systemic and portal plasma samples of mice receiving a portal drained fat transplant (pTx) and in sham-operated mice after 3 h of fasting. Results are the mean ± SEM of five to six animals.

Mentions: The development of hepatic insulin resistance is often associated with hepatic steatosis and Kupffer cell activation (12). Thus, hepatic lipid contents as well as expression levels of tissue macrophage markers were assessed. Histological examinations and biochemical determination of total hepatic lipid content was similar in sham-operated and peritoneal-transplanted mice (Fig. 4A). Moreover, no increased infiltration/activation of hepatic Kupffer cells was detected (Fig. 4B). Consistent with the absence of hepatic steatosis in portal-transplanted mice, no differences in systemic and portal plasma FFA levels were found in both groups of mice (Fig. 4C). Similarly, no difference in circulating adiponectin and leptin levels occurred (Table 1.). Thus, transplantation of fat pads to sites drained by the portal vein induces hepatic insulin resistance independently of hepatic steatosis and Kupffer cell infiltration/activation.


The portal theory supported by venous drainage-selective fat transplantation.

Rytka JM, Wueest S, Schoenle EJ, Konrad D - Diabetes (2010)

A: Left panel: Hematoxylin- and eosin-stained liver sections from sham-operated and pTx mice. Right panel: Total liver lipids were determined and expressed relative to liver weight. Results represent the mean ± SEM of four to six mice of each group. B: mRNA expression of indicated markers in liver tissue of sham-operated and pTx mice was analyzed. Results are the mean ± SEM of five mice per group, expressed relative to sham-operated mice and normalized to expression of 18S. C: FFA levels were determined in systemic and portal plasma samples of mice receiving a portal drained fat transplant (pTx) and in sham-operated mice after 3 h of fasting. Results are the mean ± SEM of five to six animals.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3012197&req=5

Figure 4: A: Left panel: Hematoxylin- and eosin-stained liver sections from sham-operated and pTx mice. Right panel: Total liver lipids were determined and expressed relative to liver weight. Results represent the mean ± SEM of four to six mice of each group. B: mRNA expression of indicated markers in liver tissue of sham-operated and pTx mice was analyzed. Results are the mean ± SEM of five mice per group, expressed relative to sham-operated mice and normalized to expression of 18S. C: FFA levels were determined in systemic and portal plasma samples of mice receiving a portal drained fat transplant (pTx) and in sham-operated mice after 3 h of fasting. Results are the mean ± SEM of five to six animals.
Mentions: The development of hepatic insulin resistance is often associated with hepatic steatosis and Kupffer cell activation (12). Thus, hepatic lipid contents as well as expression levels of tissue macrophage markers were assessed. Histological examinations and biochemical determination of total hepatic lipid content was similar in sham-operated and peritoneal-transplanted mice (Fig. 4A). Moreover, no increased infiltration/activation of hepatic Kupffer cells was detected (Fig. 4B). Consistent with the absence of hepatic steatosis in portal-transplanted mice, no differences in systemic and portal plasma FFA levels were found in both groups of mice (Fig. 4C). Similarly, no difference in circulating adiponectin and leptin levels occurred (Table 1.). Thus, transplantation of fat pads to sites drained by the portal vein induces hepatic insulin resistance independently of hepatic steatosis and Kupffer cell infiltration/activation.

Bottom Line: In the present study, we used a fat transplantation paradigm to (artificially) increase intra-abdominal fat mass to test the hypothesis that venous drainage of fat tissue determines its impact on glucose homeostasis.Epididymal fat pads of C57Bl6/J donor mice were transplanted into littermates, either to the parietal peritoneum (caval/systemic venous drainage) or, by using a novel approach, to the mesenterium, which confers portal venous drainage.These results demonstrate that the metabolic fate of intra-abdominal fat tissue transplantation is determined by the delivery of inflammatory cytokines to the liver specifically via the portal system, providing direct evidence in support of the portal hypothesis.

View Article: PubMed Central - PubMed

Affiliation: University Children’s Hospital, Zurich, Switzerland.

ABSTRACT

Objective: The "portal hypothesis" proposes that the liver is directly exposed to free fatty acids and cytokines increasingly released from visceral fat tissue into the portal vein of obese subjects, thus rendering visceral fat accumulation particularly hazardous for the development of hepatic insulin resistance and type 2 diabetes. In the present study, we used a fat transplantation paradigm to (artificially) increase intra-abdominal fat mass to test the hypothesis that venous drainage of fat tissue determines its impact on glucose homeostasis.

Research design and methods: Epididymal fat pads of C57Bl6/J donor mice were transplanted into littermates, either to the parietal peritoneum (caval/systemic venous drainage) or, by using a novel approach, to the mesenterium, which confers portal venous drainage.

Results: Only mice receiving the portal drained fat transplant developed impaired glucose tolerance and hepatic insulin resistance. mRNA expression of proinflammatory cytokines was increased in both portally and systemically transplanted fat pads. However, portal vein (but not systemic) plasma levels of interleukin (IL)-6 were elevated only in mice receiving a portal fat transplant. Intriguingly, mice receiving portal drained transplants from IL-6 knockout mice showed normal glucose tolerance.

Conclusions: These results demonstrate that the metabolic fate of intra-abdominal fat tissue transplantation is determined by the delivery of inflammatory cytokines to the liver specifically via the portal system, providing direct evidence in support of the portal hypothesis.

Show MeSH
Related in: MedlinePlus