Abstract
During the recruitment process of brown adipose tissue, the mRNA level of the fatty acyl chain elongase Elovl3 is elevated more than 200-fold in cold-stressed mice. We have obtained Elovl3-ablated mice and report here that, although cold-acclimated Elovl3-ablated mice experienced an increased heat loss due to impaired skin barrier, they were unable to hyperrecruit their brown adipose tissue. Instead, they used muscle shivering in order to maintain body temperature. Lack of Elovl3 resulted in a transient decrease in the capacity to elongate saturated fatty acyl-CoAs into very long chain fatty acids, concomitantly with the occurrence of reduced levels of arachidic acid (C20:0) and behenic acid (C22:0) in brown adipose tissue during the initial cold stress. This effect on very long chain fatty acid synthesis could be illustrated as a decrease in the condensation activity of the elongation enzyme. In addition, warm-acclimated Elovl3-ablated mice showed diminished ability to accumulate fat and reduced metabolic capacity within the brown fat cells. This points to ELOVL3 as an important regulator of endogenous synthesis of saturated very long chain fatty acids and triglyceride formation in brown adipose tissue during the early phase of the tissue recruitment.
Highlights
The process is controlled by norepinephrine release from sympathetic nerve endings found in the tissue [7, 8] and can roughly be divided into two major phases, depending on how the animal experiences the cold (4 °C)
Normal Body Temperature in Elovl3-ablated Mice—We have shown previously that Elovl3 gene expression is induced in brown adipose tissue in mice under circumstances when a high demand for heat production is required [14]
Increased Muscle Shivering in the Elovl3-ablated Mice—We have shown that, the Elovl3-ablated mice showed normal mitochondrial capacity for oxidizing fatty acids, the mice were unable to hyperactivate their brown adipose tissue in order to maintain normal body temperature at 4 °C
Summary
The VLCFA elongation activity was significantly reduced in the brown adipose tissue of Elovl3-ablated mice exposed to the cold. This phenomenon was only seen in mice during the initial cold stress. Warm-acclimated Elovl3ablated mice showed dramatically reduced lipid accumulation within the brown adipocytes as well as reduced metabolic capacity when stimulated by norepinephrine. Since the difference in lipid formation between wild-type and Elovl3-ablated mice was transient (i.e. only seen in nonstimulated and acutely stimulated tissue), it implies that ELOVL3 is a critical enzyme for lipid accumulation and metabolic activity in brown adipocytes during the early phase of the tissue recruitment
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