Albumin Deficiency Reduces Hepatic Steatosis and Improves Glucose Metabolism in a Mouse Model of Diet-Induced Obesity

Abstract

Serum albumin facilitates the transport of free fatty acids (FFAs) from adipose tissue to other organs. It was not known if impeding this process could protect from hepatic steatosis and metabolic dysfunction in obesity. We tested whether albumin knockout (Alb−/−) mice would exhibit a reduction in plasma FFA concentration, reduced hepatic lipid accumulation, and improved glucoregulation as compared to wild-type (WT) mice. Male homozygous albumin knockout mice (Alb−/−) and WT controls were fed a low-fat diet (LFD) or high-fat diet (HFD). Alb−/− mice exhibited a similar body weight gain and body composition as WT on both diets. Despite HFD-induced obesity, Alb−/− mice were protected from various comorbidities. Compared to WT mice on the HFD, Alb−/− exhibited lower plasma FFA levels, lower blood glucose levels during glucose tolerance and insulin tolerance tests, and lower hepatic steatosis and inflammation. Alb−/− mice on HFD also exhibited elevated expression of multiple genes in the liver and adipose tissues, such as peroxisome proliferator-activated receptor α in both tissues, as well as glucose transporter-4 and adiponectin in adipose tissues. The results indicate that albumin’s FFA transport function may be involved in the development of hepatic lipid accumulation and dysregulated glucose metabolism in obesity.

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

“…VCAM1 [660] has been found to influence diabetic nephropathy progression. Study demonstrated that VCAM1 [710], ALB (albumin) [715] and DPP4 [699] were essential for the induction of obesity. VCAM1 [736], ALB (albumin) [738] and DPP4 [732] are potential therapeutic targets in renal ischemia.…”

“…E2F1 [496], AGTR1 [74], VCAM1 [533], hsa-mir-7847-3p [804], FOXC1 [805], USF2 [796], YY1 [806], STAT3 [807] and BRCA1 [799] have been observed in sepsis patients. Studies have shown that E2F1 [669], VCAM1 [715], AGTR1 [83], hsa-mir-221 [780], YY1 [808], STAT3 [809], PDX1 [810] and BRCA1 [811] are associated with obesity. E2F1 [719] and VCAM1 [736] are altered expressed in patients with renal ischemia.…”

Performance evaluation of different albumin assays for the detection of analbuminemia

“…Nonetheless, it is a significant concern that unidentified substances accumulating in plasma in different patient populations could alter the behavior of BCP reagents [ 10 , 11 , 27 ]. The plasma proteome remodeling in both humans with CAA [ 25 ] and Alb -/- mice [ 20 , 21 ] is a concern in this regard. In both species, analbuminemia leads to higher expression of multiple proteins, including fibrinogen [ 20 , 25 ], and this high fibrinogen expression may lead to turbidity and thus improper spectrophotometer performance.…”

“…The plasma proteome remodeling in both humans with CAA [ 25 ] and Alb -/- mice [ 20 , 21 ] is a concern in this regard. In both species, analbuminemia leads to higher expression of multiple proteins, including fibrinogen [ 20 , 25 ], and this high fibrinogen expression may lead to turbidity and thus improper spectrophotometer performance. It should also be noted that in both BCG and BCP assays, bovine serum albumin was used as the standard for quantitation of samples.…”

“…Plasma from the albumin knockout (Alb -/- ) mouse model represents a potentially useful reference material to test the suitability of methods for detecting analbuminemia. This model was reported to have no detectable albumin expression by enzyme-linked immunosorbent assay (ELISA) and gel electrophoresis [ 18 , 19 ] and an approximately 20,000-fold reduction in albumin expression as determined by mass spectrometry (MS) [ 20 ]. With the high sensitivity of the mass spectrometry method in detecting a very small amount of albumin in the gene knockout mice, it could be reasonable to approximate this low but MS-detectable level of albumin to zero.…”