Katsuhiko Takayanagi

Mechanism of Visceral Fat Reduction in Tsumura Suzuki Obese, Diabetes (TSOD) Mice Orally Administered β-Cryptoxanthin from Satsuma Mandarin Oranges (Citrus unshiu Marc)

The carotenoid β-cryptoxanthin (β-CRX) is abundant in Satsuma mandarins (Citrus unshiu Marc). Several studies have shown a relationship between Satsuma mandarin consumption and a low risk of several diseases, for example, diabetes, gout, and hypertension, suggesting β-CRX involvement in disease prevention. We investigated the effect of β-CRX on mildly obese males. β-CRX administration reduced visceral adipose tissue, body weight, and abdominal circumference. However, the detailed mechanism by which β-CRX mediates these changes remains unknown. To identify this mechanism, we used an obese model mouse (TSOD). Oral β-CRX administration repressed body weight, abdominal adipose tissue weight, and serum lipid concentrations in TSOD; these results are identical to previous human trial results. β-CRX administration significantly repressed adipocyte hypertrophy. Gene expression analysis strongly indicated that β-CRX can alter cytokine secretion and cell proliferation. These results suggest that β-CRX derived from Satsuma mandarins can help prevent obesity by repressing hypertrophy of abdominal adipocytes.

Prevention of Adiposity by the Oral Administration of β-Cryptoxanthin

β-Cryptoxanthin (β-CRX) is a carotenoid found in human blood. It is specifically rich in Satsuma mandarin (Citrus unshiu Marc.) but very little in other fruits or vegetables. Several reports indicate the health promoting benefits of β-CRX. As we had reported visceral fat reduction on mildly obese male by the oral administration of β-CRX, a detailed mechanism has not been identified. To identify the mechanism, obese model mouse, TSOD was used in the present study. Oral administration of β-CRX repressed body weight, abdominal adipose tissue weight, and serum lipid concentrations on TSOD mice. The outstanding observation is the significant repression of adipocyte hypertrophy. DNA microarray analysis strongly indicates that the oral administration of β-CRX represses the inflammatory cytokine secretion and improves the lipid metabolism and the energy consumption. It also suggests these effects are partly mediated by PPAR-α, not only lipid metabolism and adipocyte differentiation control but possibly internal circadian clock modulation.

In Vivo and in Vitro Studies on the Absorption Characteristics of β-Cryptoxanthin in the Intestine

β-Cryptoxanthin (β-CRX) is a carotenoid abundantly present in the Satsuma mandarin (Citrus unshiu Marc.), one of the most popular fruits in Japan, and it is reported to have several health benefits. Although it is thought to have higher bioavailability than other carotenoids, the usual daily intake is small, and a good method to improve its bioavailability is needed. Hence we studied the effect of emulsification on the absorption characteristics of β-CRX in the intestine. Human trials showed that its serum transfer efficiency was statistically higher in the emulsified formulation than in fresh Satsuma mandarin juice. Caco-2 permeability studies indicated that emulsifiers preferentially accelerate the absorption of the non-esterified form of β-CRX, suggesting that emulsification is more effective for free β-CRX. This information might be useful to improve the efficiency of β-CRX serum transfer, as well as to increase the health benefits of β-CRX.

Beta-Cryptoxanthin, a Novel Carotenoid Derived from Satsuma Mandarin, Prevents Abdominal Obesity

Satsuma mandarin ( Citrus unshiu Marc.), a unique Japanese citrus species, is one of the most β-cryptoxanthin (β-CRX)-rich foods in the world. This chapter describes a study in which continuous oral administration of satsuma mandarin-derived β-CRX reduced the body weight of obese mice. Furthermore, β-CRX intake caused a significant reduction in visceral fat. A human clinical trial to evaluate the efficacy of β-CRX was carried out in mildly obese men: results revealed that β-CRX decreased visceral fat, body weight, and waist circumference. Further investigation using 3T3-L1 preadipocytes revealed that β-CRX prevents preadipocyte maturation, adipocyte hypertrophy, and lipid accumulation in mature adipocytes. We also found these effects to be canceled by the addition of LE540, a pan-agonist of the retinoic acid receptor (RAR). These results indicate that β-CRX prevents adipocyte hypertrophy by downregulating peroxisome proliferator-activated receptor gamma (PPAR-γ) via RAR and suppressing mastocytosis. This suggests that β-CRX is effective in obesity prevention and in improving the symptoms of metabolic syndromes.