TY - JOUR
T1 - Improved glucose tolerance in mice receiving intraperitoneal transplantation of normal fat tissue
AU - Konrad, D.
AU - Rudich, A.
AU - Schoenle, E. J.
N1 - Funding Information:
Acknowledgements This work was supported by grants from the Medical Faculty of the University of Zurich and the Swiss National Science Foundation grant no. 310000-112275 (to D. Konrad). We would like to greatly acknowledge I. Shai from the S. Daniel Abraham International Center for Health and Nutrition, Ben-Gurion University for valuable input and guidance in the statistical analysis of our data and M. Arras for her expert veterinary advice.
PY - 2007/4/1
Y1 - 2007/4/1
N2 - Aims/hypothesis: The association between increased (visceral) fat mass, insulin resistance and type 2 diabetes mellitus is well known. Yet, it is unclear whether the mere increase in intra-abdominal fat mass, or rather functional alterations in fat tissue in obesity contribute to the development of insulin resistance in obese patients. Here we attempted to isolate the metabolic effect of increased fat mass by fat tissue transplantation. Methods: Epididymal fat pads were removed from male C57Bl6/J mice and transplanted intraperitoneally into male littermates (recipients), increasing the combined perigonadal fat mass by 50% (p<0.005). At 4 and 8 weeks post-transplantation, glucose and insulin tolerance tests were performed, and insulin, NEFA and adipokines measured. Results: Circulating levels of NEFA, adiponectin and leptin were not significantly different between transplanted and sham-operated control mice, while results of the postprandial insulin tolerance test were similar between the two groups. In contrast, under fasting conditions, the mere increase in intra-abdominal fat mass resulted in decreased plasma glucose levels (6.9±0.4 vs 8.1±0.3 mmol/l, p=0.03) and a ∼20% lower AUC in the glucose tolerance test (p=0.02) in transplanted mice. Homeostasis model assessment of insulin resistance (HOMA-IR) was 4.1±0.4 in transplanted mice (vs 6.2±0.7 in sham-operated controls) (p=0.02), suggesting improved insulin sensitivity. Linear regression modelling revealed that while total body weight positively correlated, as expected, with HOMA-IR (β: 0.728, p=0.006), higher transplanted fat mass correlated with lower HOMA-IR (β: -0.505, p=0.031). Conclusions/interpretation: Increasing intra-abdominal fat mass by transplantation of fat from normal mice improved, rather than impaired, fasting glucose tolerance and insulin sensitivity, achieving an effect opposite to the expected metabolic consequence of increased visceral fat in obesity.
AB - Aims/hypothesis: The association between increased (visceral) fat mass, insulin resistance and type 2 diabetes mellitus is well known. Yet, it is unclear whether the mere increase in intra-abdominal fat mass, or rather functional alterations in fat tissue in obesity contribute to the development of insulin resistance in obese patients. Here we attempted to isolate the metabolic effect of increased fat mass by fat tissue transplantation. Methods: Epididymal fat pads were removed from male C57Bl6/J mice and transplanted intraperitoneally into male littermates (recipients), increasing the combined perigonadal fat mass by 50% (p<0.005). At 4 and 8 weeks post-transplantation, glucose and insulin tolerance tests were performed, and insulin, NEFA and adipokines measured. Results: Circulating levels of NEFA, adiponectin and leptin were not significantly different between transplanted and sham-operated control mice, while results of the postprandial insulin tolerance test were similar between the two groups. In contrast, under fasting conditions, the mere increase in intra-abdominal fat mass resulted in decreased plasma glucose levels (6.9±0.4 vs 8.1±0.3 mmol/l, p=0.03) and a ∼20% lower AUC in the glucose tolerance test (p=0.02) in transplanted mice. Homeostasis model assessment of insulin resistance (HOMA-IR) was 4.1±0.4 in transplanted mice (vs 6.2±0.7 in sham-operated controls) (p=0.02), suggesting improved insulin sensitivity. Linear regression modelling revealed that while total body weight positively correlated, as expected, with HOMA-IR (β: 0.728, p=0.006), higher transplanted fat mass correlated with lower HOMA-IR (β: -0.505, p=0.031). Conclusions/interpretation: Increasing intra-abdominal fat mass by transplantation of fat from normal mice improved, rather than impaired, fasting glucose tolerance and insulin sensitivity, achieving an effect opposite to the expected metabolic consequence of increased visceral fat in obesity.
KW - Fat transplantation
KW - Glucose homeostasis
KW - Insulin resistance
KW - Insulin sensitivity
KW - Obesity
KW - Visceral adiposity
UR - http://www.scopus.com/inward/record.url?scp=33847637510&partnerID=8YFLogxK
U2 - 10.1007/s00125-007-0596-1
DO - 10.1007/s00125-007-0596-1
M3 - Article
AN - SCOPUS:33847637510
SN - 0012-186X
VL - 50
SP - 833
EP - 839
JO - Diabetologia
JF - Diabetologia
IS - 4
ER -
