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


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.
University Children’s Hospital, Zurich, Switzerland.
Julia M
JM
Rytka
Stephan
S
Wueest
Eugen J
EJ
Schoenle
Daniel
D
Konrad
D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000637:transplantation*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers; D004822:Epididymis; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000378:metabolism; D006946:Hyperinsulinism / Q000097:blood; D007249:Inflammation / Q000235:genetics; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000172:deficiency; D050152:Intra-Abdominal Fat / Q000637:transplantation*; D020738:Leptin / Q000097:blood; D008297:Male; D008643:Mesentery / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010537:Peritoneum / Q000601:surgery; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D052242:Adiponectin; D001786:Blood Glucose; D016207:Cytokines; D017931:DNA Primers; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D012333:RNA, Messenger; D012313:RNA