Oxytocin (OXT) and OXT receptor (OXTR) have been implicated in the regulation of energy homeostasis, but the detailed mechanism is still unclear. We recently showed late-onset obesity and impaired cold-induced thermogenesis in male OXTR knockout (Oxtr^−/−) mice. Here we demonstrate that the OXTR in the hypothalamus has important functions in thermoregulation. Male Oxtr^−/− mice failed to maintain their body temperatures during exposure to a cold environment. Oxtr^−/− mice also showed decreased neuronal activation in the thermoregulatory hypothalamic region during cold exposure. Normal cold-induced thermogenesis was recovered in Oxtr^−/− mice by restoring OXTR to the hypothalamus with an adeno-associated virus-Oxtr vector. In addition, brown adipose tissue (BAT) in Oxtr^−/− mice contained larger lipid droplets in both 10- and 20-week-old compared with BAT from age-matched Oxtr^+/+ control mice. In BAT, the expression level of β3-adrenergic receptor at normal temperature was lower in Oxtr^−/− mice than that in control mice. In contrast, α2A-adrenergic receptor expression level was higher in BAT from Oxtr^−/− mice in both normal and cold temperatures. Because β3- and α2A-adrenergic receptors are known to have opposite effects on the thermoregulation, the imbalance of adrenergic receptors is suspected to affect this dysfunction in the thermoregulation. Our study is the first to demonstrate that the central OXT/OXTR system plays important roles in the regulation of body temperature homeostasis.

Aim: We assessed levels of polyunsaturated fatty acid (PUFA) in serum and red blood cells (RBCs) among groups stratified by generation and its clinical significance in Japanese subjects living in an urban area. Methods: We enrolled 200 apparently healthy Japanese (126 males, mean age: 50.3±9.2 years) living in an urban area. Levels of PUFA, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-gamma-linolenic acid (DGLA) in serum and RBCs were measured for each generation (G1 <35y, G2 35y-<45y, G3 45y-<55y, G4 55y-<65y, G5≥65y). Results: No significant differences in EPA, DHA, AA, or EPA/AA were observed between males and females. After dividing into generations, stepwise increases in EPA and DHA, but not DGLA or AA, were observed in serum (all p<0.0001). EPA/AA ratios were stepwisely increased in serum (mean: G1:0.26, G2:0.29, G3:0.43, G4:0.58, G5:0.68, p<0.0001) and RBCs (mean: G1:0.10, G2:0.09, G3:0.15, G4:0.20, G5:0.23, p<0.0001). Positive correlations of EPA (r=0.83), DHA (r=0.55), DGLA (r=0.54), AA (r=0.29), and EPA/AA (r=0.91) were demonstrated between serum and RBCs. In addition, a significant positive correlation between EPA/AA ratios and insulin sensitivity as well as a negative correlation between those ratios and insulin resistance were observed in subjects with metabolic syndrome. Conclusion: Low levels of EPA/AA, which were associated with insulin resistance, were demonstrated in young Japanese adults living in an urban area.

Nonalcoholic fatty liver disease (NAFLD) is the preferred term to describe the spectrum of liver damage ranging from hepatic steatosis to steatohepatitis, liver fibrosis, and cirrhosis, and it is emerging as the most common liver disease in industrialized countries. Thus, the discovery of food components that would ameliorate NAFLD is of interest. Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of linoleic acid, has attracted considerable attention because of its potentially beneficial biological effects both in vitro and in vivo. We tested whether dietary CLA protects Zucker (fa/fa) rats from hepatic injury. After 8 wk of feeding, hepatomegaly, hepatic triglyceride (TG) accumulation, and elevated hepatic injury markers in plasma were markedly alleviated in CLA-fed Zucker rats compared with linoleic acid-fed (control) rats. These effects were attributed in part to the enhanced hepatic activities of carnitine palmitoyltransferase, a key enzyme of fatty acid β-oxidation, and microsomal TG transfer protein, an important factor for lipoprotein secretion due to the CLA diet. We previously reported that the severe hyperinsulinemia in control Zucker rats was attenuated in CLA-fed rats due to an enhanced level of plasma adiponectin, which improves insulin sensitivity. In the present study, the adiponectin concentration was increased and the mRNA expression of tumor necrosis factor-α, an inflammatory cytokine, was markedly suppressed in the liver of CLA-fed Zucker rats. We speculate that the enhanced level of liver adiponectin may prevent the development and progression of NAFLD in CLA-fed Zucker rats.