Protection from obesity and insulin resistance in mice overexpressing human apolipoprotein C1.

Abstract

Apolipoprotein (APO) C1 is a 6.6-kDa protein present in plasma and associated with lipoproteins. Using hyperinsulinemic-euglycemic clamp tests, we previously found that in APOC1 transgenic mice, the whole-body insulin-mediated glucose uptake is increased concomitant with a decreased fatty acid uptake. These latter results are confirmed in the present study, showing that APOC1 transgenic mice exhibit a 50% reduction in the uptake of the fatty acid analog 15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid in white adipose tissue stores. We next investigated whether APOC1 overexpression can modulate the initiation and/or development of obesity and insulin resistance. When crossbred on the genetically obese ob/ob background, APOC1 transgenic mice were fully protected from the development of obesity compared with ob/ob only mice, as reflected by a strong reduction in body weight (21 +/- 4 vs. 44 +/- 7 g), total adipose tissue stores (15 +/- 3 vs. 25 +/- 3% body wt), and average adipocyte size (7,689 +/- 624 vs. 15,295 +/- 1,289 microm(2)). Although less pronounced, APOC1 overexpression also reduced body weight on a wild-type background, solely due to a reduction in adipose tissue. Furthermore, despite elevated plasma free fatty acid and triglyceride levels, APOC1 overexpression significantly improved insulin sensitivity in ob/ob mice, as demonstrated by a strong reduction in plasma glucose and insulin levels, as well as a better performance in the glucose tolerance test. In conclusion, a marked reduction in the uptake of fatty acids into adipocytes may underlie the protection from obesity and insulin resistance in transgenic mice overexpressing human APOC1.

• Authors: M C Jong, P J Voshol, M Muurling, V E Dahlmans, J A Romijn, H Pijl, L M Havekes
• Journal: Diabetes (Diabetes) Vol. 50 Issue 12 Pg. 2779-85 (Dec 2001) ISSN: 0012-1797 [Print] United States
• PMID: 11723061 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Apolipoprotein C-I
• Apolipoproteins C
• Blood Glucose
• Fatty Acids
• Fatty Acids, Nonesterified
• Insulin
• Iodine Radioisotopes
• Iodobenzenes
• Triglycerides
• iodofiltic acid
• Cholesterol

Topics

• Adipocytes (pathology)
• Adipose Tissue (metabolism, pathology)
• Animals
• Apolipoprotein C-I
• Apolipoproteins C (genetics, physiology)
• Blood Glucose (analysis)
• Cell Size
• Cholesterol (blood)
• Crosses, Genetic
• Fatty Acids (metabolism)
• Fatty Acids, Nonesterified (blood)
• Gene Expression
• Glucose Tolerance Test
• Humans
• Insulin (blood)
• Insulin Resistance (genetics)
• Iodine Radioisotopes
• Iodobenzenes (metabolism)
• Male
• Mice
• Mice, Obese
• Mice, Transgenic
• Obesity (genetics, pathology)
• Organ Size
• Triglycerides (blood)
• Weight Loss (genetics)