Aim: Adiponectin has insulin-sensitizing, anti-atherogenic, and anti-inflammatory properties, and researchers have recently reported that -3 polyunsaturated fatty acid (PUFA) can increase the serum adiponectin concentration, suggesting that dietary factors, such as fish intake, may have an influence on the serum adiponectin concentration. In general, Japanese subjects consume twice as much fish as people in other countries. We hypothesized that incremental change in serum -3 PUFA levels by fish intake is an important regulator of serum adiponectin even in Japanese subjects. The aim of this study was to explore the relationship among fish consumption, serum -3 PUFA, such as eicosapentaenoic acid (EPA), levels, and serum adiponectin levels. Method: We recruited 17 healthy Japanese volunteers (seven men and 10 women) for an 8-week fishdiet intervention ( -3 PUFA 3.0 g/day) without affecting total energy intake, and measured serum adiponectin concentration and fatty acid profiles. Results: Fish-diet intervention significantly increased the serum adiponectin concentration in women (from 13.5 4.6 to 15.8 5.2 g/mL, p 0.01) but not in men (from 8.7 2.8 to 8.7 2.5 g/mL). Serum -3 PUFA increased more in female subjects than male subjects after the fish-diet intervention (57.3 86.6 vs 150.9 46.7 g/mL, p 0.011), suggesting that changes in -3 PUFA concentration may explain the different response between sexes. Conclusion: A fish-based diet intervention increased the serum adiponectin concentration in young, non-obese, healthy Japanese female subjects. The increment in serum -3 PUFA may regulate the serum adiponectin concentration. J Atheroscler Thromb, 2010; 17:628-637.

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AP-2beta modulated the expression of leptin through direct interaction with its promoter region.

Abstract. Abnormal secretion of adipocytokines promotes atherosclerosis, diabetes and insulin resistance, and is mainly induced by adipocyte hypertrophy. Recently, the circulating adipocytokine concentrations were reported to change in the postprandial period, as the levels of TNFα, IL-6 IL-8 and McP-1 increased after a meal, whereas that of adiponectin decreased. These data suggest that prandial modulation of cytokines may be involved in the pathogenesis of atherosclerosis in type 2 diabetes. However, the regulatory mechanism of such change is still unclear. In the present study, we identified this mechanism with a special focus on the functions of protein kinase c (PKc) and of the transcription factor AP-2β, both of which are associated with the pathophysiology of adipocytokine regulation. PKcµ was highly phosphorylated in the re-feeding condition compared to the fasting condition in mouse adipose tissue, while other PKc isoforms remained unchanged. Furthermore, overexpression of PKcµ in 3T3-L1 adipocytes, but not other PKc isoforms, positively regulated the mRNA expression and promoter activity of McP-1 and IL-6, and negatively regulated those of adiponectin. AP-2β had similar effects on the expression and promoter activity of these adipocytokines. Interestingly, overexpression of PKcµ enhanced the stimulatory and inhibitory effects of AP-2β on the expression of these adipocytokines. Finally, PKcµ could not activate a mutant McP-1 promoter lacking the AP-2β binding domain. Our results suggest that postprandial activation of PKcµ plays a role in disordered postprandial adipocytokine expression through AP-2β.

Summary A 17-year-old boy was referred to our endocrinology clinic for a clinical investigation of hyperinsulinemia. An oral glucose tolerance test showed plasma glucose concentrations in the normal range. However, insulin concentrations were considerably elevated (0 min: 71 μU/mL; 60 min: 953 μU/mL), suggesting severe insulin resistance. An insulin tolerance test confirmed that he had insulin resistance. There was no apparent hormonal or metabolic cause, including obesity. The patient had no outward features of hyperinsulinemia, including acanthosis nigricans or hirsutism. However, his mother and grandfather also had hyperinsulinemia. Genetic testing showed that the patient (proband), his mother, and his grandfather had a novel p.Val1086del heterozygous mutation in exon 17 of the insulin receptor gene (INSR). Although all three family members have the same mutation, their clinical courses have been different. The onset of the mother’s diabetes was estimated at 50 years, whereas the grandfather developed diabetes at 77 years. Learning points Type A insulin resistance syndrome is caused by mutations in the insulin receptor (INSR) gene and results in severe insulin resistance. Genetic evaluation should be considered in adolescents or young adults with dysglycemia when an atypical phenotype, such as severe insulin resistance, or a relevant family history is observed. Clinical courses may differ even if the same genetic mutation is found in a family.