The Portal Theory Supported by Venous Drainage-Selective Fat Transplantation

• Published in: Diabetes (New York, N.Y.) Vol. 60; no. 1; pp. 56 - 63
• Main Authors: RYTKA, Julia M, WUEEST, Stephan, SCHOENLE, Eugen J, KONRAD, Daniel
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.01.2011
• Subjects: Abdomen; Adiponectin - blood; Adipose Tissue - transplantation; Animals; Biological and medical sciences; Blood Glucose - metabolism; Body fat; Care and treatment; Complications and side effects; Cytokines; Cytokines - genetics; Diabetes; Diabetes. Impaired glucose tolerance; DNA Primers; Drainage; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epididymis; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty acids; Fatty Acids, Nonesterified - blood; Glucose; Glucose Clamp Technique; Glucose Intolerance - metabolism; Glucose metabolism; Homeostasis; Hyperinsulinism - blood; Hypotheses; Inflammation - genetics; Insulin - blood; Insulin Resistance; Interleukin-6 - deficiency; Intra-Abdominal Fat - transplantation; Leptin - blood; Lipids; Liver; Male; Medical sciences; Mesentery - surgery; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Observations; Peritoneum - surgery; Plasma; Properties; Research design; Reverse Transcriptase Polymerase Chain Reaction; Risk factors; RNA - genetics; RNA - isolation & purification; RNA, Messenger - genetics; Tissue transplantation; Transplantation of organs, tissues, etc; Veins; Veins & arteries; Switzerland; Netherlands; Endocrinopathy; Transplantation; Support; Diabetes mellitus
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db10-0697

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. 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. 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. 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.