COMMENTARIES

Prevention of Metabolic Syndrome by Dietary Manipulation

Koji Nagao, Laboratory of Nutrition Biochemistry, Department of Applied Biological Sciences, Saga University, Honjo-1, Saga 840-8502, Japan, Email: knagao@cc.saga-u.ac.jp

Koji Nagao

Lifestyle-related diseases, such as obesity, hyperlipidemia, atherosclerosis, type 2 diabetes, and hypertension, are widespread and increasingly prevalent in industrialized countries. Accompanied by the rapid increase in the number of elderly people, this becomes a medical and a socioeconomic issue. A clustering of metabolic disorders (in particular abdominal obesity, hypertriglyceridemia, a low level of high density lipoprotein cholesterol, hypertension, and high fasting glucose levels) in an individual, defined as metabolic syndrome, is known to increase cardiovascular morbidity and mortality. Although the pathogenesis of metabolic syndrome is complicated and precise details of the underlying mechanisms are not known, it has been suggested that the quality of dietary lipids may be an important modulator in terms of the risks associated with this syndrome [1]. Animal studies and clinical trials have revealed different effects of individual dietary lipids, such as n-3 polyunsaturated fatty acids (PUFAs), conjugated fatty acids (CFAs), sterols, medium-chain fatty acids (MCFAs), diacylglycerols (DAG), and phospholipids (PLs).

 

n-3 PUFAs

It is well known that the consumption of n-3 PUFAs, such as linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid, is correlated with a reduced risk of cancer and cardiovascular disease in clinical and animal studies [1,2]. Recently, regulation of adipocytokine production by n-3 PUFAs has attracted considerable attention. It has been reported that dietary EPA and DHA increased adiponectin secretion in mice, and treatment with EPA increased plasma adiponectin in human obese subjects [1].

 

CFAs

Since the discovery of conjugated linoleic acid (CLA) as a grilled beef-derived antimutagen in the 1980s, about half of the studies concerning physiological functions of CFAs have been focused on their anticarcinogenic properties. However, there is an increasing number of reports of the antiobesity, antiatherogenic, antidiabetic, and hypotensive properties of CFAs in animal and human studies [3-7]. Additionally, our recent studies indicate that dietary CLA can alleviate metabolic disorders through the regulation of adipocytokine productions in animal models [8-12].

 

Sterols

Plant sterols and stanols are chemical homologs of cholesterol that are abundant in vegetable oils and whole grains, and their cholesterol-lowering activity, in particular the effects of sitosterol and sitostanol, have been well established in a number of human studies [1]. Recently, campest-5-en-3-one (campestenone), a 3-oxo derivative of campesterol, has been reported to reduce body fat and serum lipids through the suppression of lipogenesis, enhancement of lipolysis and increase of energy expenditure [13].

 

MCFAs

MCFAs, which generally consist of C6-10, are found in coconut oil and palm kernel oil. Since the 1950s, medium-chain triglyceride (MCT) has been used for the dietary treatment of malabsorption syndrome because of its metabolic properties. Recently, structured medium-chain and long-chain triacylglycerol (MLCT) containing MCFA and a long-chain fatty acid in the same molecule, has been developed. Healthy subjects consumed MLCT daily at breakfast for 12 weeks, and significant decreases of body weight, amount of body fat, subcutaneous and visceral fat were noted at 8 weeks [1]. Alleviation of obesity and glucose tolerance through the enhancement of adiponectin production by MCT diet has been also reported [1].

 

DAG

Various fats and oils contain DAG as a minor constituent. Several human studies showed that DAG oil, rich in the 1,3-DAG isoform, suppressed postprandial hypertriglycerolemia and reduced body fat mass compared with the corresponding triacylglycerol (TAG) oil [1]. In addition, DAG reduced postprandial hyperlipidemia and ameliorated glucose intolerance in obese rats through, in part, increased levels of serum adiponectin [1].

 

Phospholipids

Growing evidence indicates that dietary PLs have beneficial effects compared with dietary TAG [1,14,15]. Recently, we reported that feeding of n-3 PUFA rich-phosphatidylcholine or phosphatidylinositol alleviate obesity-related disorders with enhanced serum adiponectin levels in obese rats [16,17].

 

Conclusions             

We recognize that dietary lipids act as sources of energy, cell structure, and signaling molecules, as well as regulators of nutrient metabolism and cell functions by the control of gene expression. Such regulatory lipids can be defined as “bioactive lipids” and they suppress the accumulation of abdominal adipose tissue and lipids in the liver and serum, and alleviate hypertension and type 2 diabetes through the transcriptional regulation of lipid and glucose metabolism [1]. Peroxisome proliferator-activated receptors, sterol regulatory element binding proteins, liver X receptor?α, retinoid X receptor? α, farnesoid X receptor?α, hepatic nuclear factor 4α, and nuclear factor κB contribute to these nuclear actions of bioactive lipids with complex interactions [1]. Additionally, recent studies demonstrate the striking ability of bioactive lipids, such as n-3 PUFA, CLA, MCT, DAG, and phospholipids, to regulate the production of physiologically active adipocytokines. In particular, the function of bioactive lipids as dietary adiponectin inducers (dietary insulin sensitizers) deserves attention with respect to alleviation of metabolic syndrome by dietary manipulation.

References

  1.    Nagao K, Yanagita T. 2008. Bioactive lipids in metabolic syndrome. Prog Lipid Res 47: 127-46.
  2.    Buang Y, Cha JY, Nagao K, Wang YM, Inoue N, Yanagita T. 2004. Alleviation of fatty liver by alpha-linolenic acid. J Nutr Sci Vitaminol 50: 272-76.
  3.    Nagao K, Yanagita T. 2005. Conjugated fatty acids in food and their health benefits. J Biosci Bioeng 100: 152-57.
  4.    Nagao K, Wang YM, Inoue N, Han, et al. 2003. The 10trans,12cis isomer of conjugated linoleic acid promotes energy metabolism in OLETF rats. Nutrition 19: 652-56.
  5.    Arao K, Yotsumoto H, Han SY, Nagao K, Yanagita T. 2004. The 9cis,11trans,13cis isomer of conjugated linolenic acid reduces apolipoprotein B100 secretion and triacylglycerol synthesis in HepG2 cells. Biosci Biotechnol Biochem 68: 2643-45.
  6.    Arao K, Wang YM, Inoue N, et al. 2004. Dietary effect of pomegranate seed oil rich in 9cis,11trans,13cis conjugated linolenic acid on lipid metabolism in obese, hyperlipidemic OLETF Rats. Lipids Health Dis 3(24): 1-7.
  7.    Wang YM, Nagao K, Inoue N, et al. 2006. Isomer-specific anti-obese and hypolipidemic properties of conjugated linoleic acid in obese OLETF rats. Biosci Biotechnol Biochem 70: 355-62.
  8.    Nagao K., Inoue N, Wang YM, et al. 2003. The 10trans,12cis isomer of conjugated linoleic acid suppresses the development of hypertension in Otsuka Long-Evans Tokushima Fatty rats. Biochem Biophys Res Commun 306: 134-38.
  9.    Nagao K, Inoue N, Wang YM, Yanagita T. 2003. Conjugated linoleic acid enhances plasma adiponectin level and alleviates hyperinsulinemia and hypertension in Zucker diabetic fatty (fa/fa) rats. Biochem Biophys Res Commun 310: 562-66.
  10.    Inoue N, Nagao K, Hirata J, Wang YM, Yanagita T. 2004. Conjugated linoleic acid prevents the development of essential hypertension in spontaneously hypertensive rats. Biochem Biophys Res Commun 323: 679-84.
  11.    Nagao K, Inoue N, Wang YM, Shirouchi B, Yanagita T. 2005. Dietary conjugated linoleic acid alleviates nonalcoholic fatty liver disease in Zucker (fa/fa) rats. J Nutr 135: 9-13.
  12.    Inoue N, Nagao K, Wang YM, Noguchi H, Shirouchi B, Yanagita T. 2006. Dietary conjugated linoleic acid lowered tumor necrosis factor-alpha content and altered expression of genes-related to lipid metabolism and insulin sensitivity in the skeletal muscle of Zucker rats. J Agric Food Chem 54: 7935-39.
  13.    Ikeda I, Konno R, Shimizu T, et al. 2006. Campest-5-en-3-one, an oxidized derivative of campesterol, activates PPAR?, promotes energy consumption and reduces visceral fat deposition in rats. Biochim. Biophys. Acta 1760: 800-807.
  14.    Yanagita T, Nagao K. 2008. Functional lipids and prevention of metabolic syndrome. Asia Pac J Clin Nutr 17: 189-91.
  15.    Buang Y, Wang YM, Cha JY, Nagao K, Yanagita Y. 2005. Dietary Phosphatidylcholine alleviates fatty liver induced by orotic acid. Nutrition 21; 867-73.
  16.    Shirouchi B, Nagao K, Inoue N, Ohkubo T, Hibino H, Yanagita T. 2007. Effect of dietary omega 3-PC on obesity-related disorders in obese OLETF rats. J Agric Food Chem 55: 7170-76.
  17.    Shirouchi B, Nagao K, Inoue N, et al. 2008. Dietary phosphatidylinositol prevents the development of nonalcoholic fatty liver disease in Zucker (fa/fa) rats. J Agric Food Chem 56: 2375-79.

 

 

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