J Nutr. 2014 Feb;144(2):164-9.

Wax esters from the marine copepod Calanus finmarchicus reduce diet-induced obesity and obesity-related metabolic disorders in mice.

Höper AC, Salma W, Sollie SJ, Hafstad AD, Lund J, Khalid AM, Raa J, Aasum E, Larsen TS.

Cardiovascular Research Group, Institute of Medical Biology, Faculty of Health Sciences.

 

Abstract

We showed previously that dietary supplementation with oil from the marine zooplankton Calanus finmarchicus (Calanus oil) attenuates obesity, inflammation, and glucose intolerance in mice. More than 80% of Calanus oil consists of wax esters, i.e., long-chain fatty alcohols linked to long-chain fatty acids. In the present study, we compared the metabolic effects of Calanus oil-derived wax esters (WE) with those of purified eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) ethyl esters (E/D) in a mouse model of diet-induced obesity. C57BL/6J mice received a high-fat diet (HFD; 45% energy from fat). After 7 wk, the diet was supplemented with either 1% (wt:wt) WE or 0.2% (wt:wt) E/D. The amount of EPA + DHA in the E/D diet was matched to the total amount of n–3 (v-3) polyunsaturated fatty acids (PUFAs) in the WE diet. A third group was given an unsupplemented HFD throughout the entire 27-wk feeding period. WE reduced body weight gain, abdominal fat, and liver triacylglycerol by 21%, 34%, and 52%, respectively, and significantly improved glucose tolerance and aerobic capacity. In abdominal fat depots, WE reduced macrophage infiltration by 74% and downregulated expression of proinflammatory genes (tumor necrosis factor-a, interleukin–6, and monocyte chemoattractant protein–1), whereas adiponectin expression was significantly upregulated. By comparison, E/D primarily suppressed the expression of proinflammatory genes but had less influence on glucose tolerance thanWE. E/D affected obesity parameters, aerobic capacity, or adiponectin expression by <10%. These results show that the wax ester component of Calanus oil can account for the biologic effects shown previously for the crude oil. However, these effects cannot exclusively be ascribed to the content of n–3 PUFAs in the wax ester fraction.

PMID: 24285691

 

Supplement

There is considerable evidence indicating that obesity is a contributing factor for major metabolic disorders, such as insulin resistance, diabetes and fatty liver disease, which in combination with cardiovascular disease and hypertension increase the global risk of cardiovascular disease. Current evidence suggests that obesity, in particular abdominal obesity, is associated with a chronic local low-grade inflammation (1). In this process the enlarged/expanded adipocytes start to secrete pro-inflammatory molecules (such as tumor necrosis factor alpha, interleukin -6, interleukin-1β and monocyte chemoattractant protein-1), which in turn lead to inflammation and metabolic dysfunction (2, 3).

During the past 30 years, however, seafood and marine oils have been shown to have a number of health benefits (4) (e.g. prevention of atherosclerosis, thrombosis, hypertriglyceridemia and hypertension), which have first and foremost been associated with two typical marine omega-3 polyunsaturated fatty acids (n-3 PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

 

Figure 1

Figure 1: Photograph of the copepod Calanus finmarchicus. Its oil contains a unique combination of several high-valued long-chain fatty acids, fatty alcohols and natural antioxidants such as astaxanthin.

 

Calanus oil has recently emerged as a product for the human market. It is extracted from the copepod Calanus finmarchicus, the dominant marine zooplankton species in North Atlantic waters (5). This copepod crustacean is 3-4 mm in body length (Figure 1). Its oil contains a unique combination of several high-valued long-chain fatty acids, fatty alcohols and natural antioxidants such as astaxanthin. In contrast to krill oil and traditional fish oils, where lipids are predominantly bound as phospholipids and triacylglycerols (TAGs), respectively, lipids in Calanus oil are mainly comprised of esters of long-chain fatty acids and fatty alcohols, usually termed wax esters (Figure 2).

 Figure 3

Figure 2: A typical wax ester in Calanus oil with the polyunsaturated omega-3 fatty acid SDA (18:4 n-3) and a long-chain monounsaturated alcohol (22:1 n-11)

 

In a previous study (6) we demonstrated that dietary supplementation with Calanus oil reduced abdominal fat deposition in mice receiving an energy rich diet. Besides, it antagonized glucose intolerance and local, low-grade inflammation in adipose tissue which are both characteristics of obesity. The questions asked in this study were whether the content of wax ester in crude Calanus oil can account for its beneficial effects and, if so, whether these effects can be solely attributed to the content of n-3 PUFA in the wax ester fraction.

In order to answer these questions three groups of mice were given an energy rich diet for 27 weeks in order to make them obese. After 7 weeks the diet for one of the groups was supplemented with Calanus oil-derived wax ester (1 g/100 g), whereas another group received purified EPA/DHA matching the amount of omega-3 polyunsaturated fatty acids in the wax ester diet. The third group was given un-supplemented diet for entire feeding period.

 

Figure 2

Figure 3: Representative images of macrophage infiltration F4/80 staining (A), number of crown like structures, CLSs (B), total number of macrophages (C), and F4/80 mRNA expression (D) in perirenal adipose tissue from mice fed un-supplemented high fat diet (HFD), or HFD supplemented with EPA/DHA (E/D), or Calanus oil-derived wax ester (WE) for 27 wk. The mRNA expression is normalized to levels found in HFD. Values are means ± SEMs, n = 4–7 per group. Labeled means without a common letter differ, P < 0.05.

 

The results show that dietary supplementation with wax ester had the same effect as crude Calanus oil in terms of preventing abdominal and hepatic fat deposition. Also, it effectively improved glucose tolerance and reduced the inflammatory state in adipose tissue (Fig. 3). Dietary supplementation with EPA/DHA suppressed the expression of pro-inflammatory genes and improved glucose tolerance, although not to the same extent as wax ester. On the other hand, it did not significantly affect obesity. These results show that the wax ester component of Calanus oil can account for the biological effects previously shown for the crude oil. These effects, however, cannot exclusively be ascribed to the content of n-3 PUFA in the wax ester fraction.

 

The importance of this study:

Collectively, these findings support the notion that low-grade inflammation in adipose tissue is the link between obesity and insulin resistance, and that reduction of visceral and ectopic fat mass by Calanus oil supplementation is an obvious strategy for targeting the inflammatory network. Moreover, abdominal obesity with elevated production of pro-inflammatory cytokines, and dysregulation of adipose tissue metabolism are key processes linking obesity to cardiovascular diseases.  Hence, the present results advocate further studies to find out if modification of the adipocardiovascular axis by dietary Calanus oil can provide a potential treatment for obesity-related cardiovascular diseases.

 

References:

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  6. Höper AC, Salma W, Khalid AM, Hafstad AD, Sollie SJ, Raa J, et al. Oil from the marine zooplankton Calanus finmarchicus improves the cardiometabolic phenotype of diet‐induced obese mice. British Journal of Nutrition. 2013;110(12):2186‐93.

 

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