Abstract
Stearic acid (C18:0) is a long chain dietary saturated fatty acid that has been shown to reduce metastatic tumor burden. Based on preliminary observations and the growing evidence that visceral fat is related to metastasis and decreased survival, we hypothesized that dietary stearic acid may reduce visceral fat. Athymic nude mice, which are used in models of human breast cancer metastasis, were fed a stearic acid, linoleic acid (safflower oil), or oleic acid (corn oil) enriched diet or a low fat diet ad libitum. Total body weight did not differ significantly between dietary groups over the course of the experiment. However visceral fat was reduced by ∼70% in the stearic acid fed group compared to other diets. In contrast total body fat was only slightly reduced in the stearic acid diet fed mice when measured by dual-energy x-ray absorptiometry and quantitative magnetic resonance. Lean body mass was increased in the stearic acid fed group compared to all other groups by dual-energy x-ray absorptiometry. Dietary stearic acid significantly reduced serum glucose compared to all other diets and increased monocyte chemotactic protein-1 (MCP-1) compared to the low fat control. The low fat control diet had increased serum leptin compared to all other diets. To investigate possible mechanisms whereby stearic acid reduced visceral fat we used 3T3L1 fibroblasts/preadipocytes. Stearic acid had no direct effects on the process of differentiation or on the viability of mature adipocytes. However, unlike oleic acid and linoleic acid, stearic acid caused increased apoptosis (programmed cell death) and cytotoxicity in preadipocytes. The apoptosis was, at least in part, due to increased caspase-3 activity and was associated with decreased cellular inhibitor of apoptosis protein-2 (cIAP2) and increased Bax gene expression. In conclusion, dietary stearic acid leads to dramatically reduced visceral fat likely by causing the apoptosis of preadipocytes.
Highlights
Numerous studies have identified obesity as a risk factor for postmenopausal breast cancer [1,2]
Dietary stearic acid leads to a reduction of abdominal fat and total body fat (TBF)
The percentage of TBF decreased 25% (Fig. 2 A), while the percentage of total body lean mass (TBLM) increased 4% (Fig. 2 B) in the stearic acid diet group compared to the low fat mice when measured by Dual energy X-ray absorptiometry (DXA)
Summary
Numerous studies have identified obesity as a risk factor for postmenopausal breast cancer [1,2]. A growing body of literature have found that visceral adipose tissue (VAT) is related to cancer survival [9,10,11]. This may be due to differences between VAT and other fat depots with respect to their cytokine profile which favors lipolysis, inflammation, angiogenesis, and insulin resistance [12]. In a recent study we found that dietary stearic acid reduced metastasis tumor burden in an athymic (nude) mouse breast cancer metastasis model [13]. A serendipitous observation in these studies suggested that perhaps dietary stearic acid reduced VAT. The present studies were designed to confirm and expand this observation and to begin to understand the mechanism driving these changes
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