White adipocytes are unique in that they contain large unilocular lipid droplets that occupy most of the cytoplasm. To identify genes involved in the maintenance of mature adipocytes, we expressed dominant-negative PPARγ in 3T3-L1 cells and performed a microarray screen. The fat-specific protein of 27 kDa (FSP27) was strongly downregulated in this context. FSP27 expression correlated with induction of differentiation in cultured preadipocytes, and the protein localized to lipid droplets in murine white adipocytes in vivo. Ablation of FSP27 in mice resulted in the formation of multilocular lipid droplets in these cells. Furthermore, FSP27-deficient mice were protected from diet-induced obesity and insulin resistance and displayed an increased metabolic rate due to increased mitochondrial biogenesis in white adipose tissue (WAT). Depletion of FSP27 by siRNA in murine cultured white adipocytes resulted in the formation of numerous small lipid droplets, increased lipolysis, and decreased triacylglycerol storage, while expression of FSP27 in COS cells promoted the formation of large lipid droplets. Our results suggest that FSP27 contributes to efficient energy storage in WAT by promoting the formation of unilocular lipid droplets, thereby restricting lipolysis. In addition, we found that the nature of lipid accumulation in WAT appears to be associated with maintenance of energy balance and insulin sensitivity.

When ambient temperature is decreased in mammals, autonomic and behavioral heat-gain responses occur to maintain their core temperatures. However, what molecules in cutaneous sensory nerve endings mediate cooling-induced responses is unclear. Recently, transient receptor potential melastatin-8 (TRPM8) has been identified in cell bodies of sensory neurons as low-temperature and menthol-activated cation channel. We hypothesized that TRPM8 mediates cooling-induced autonomic and behavioral heat-gain responses. To activate TRPM8 specifically, we applied 1-10% menthol to the skin of whole trunk in mice instead of cooling and measured core temperatures and autonomic and behavioral heat-gain responses. Solvent of menthol (100% ethanol) was used as control. Significant elevation of core temperatures was observed between 20 and 120 min after menthol application. Pretreatment with diclofenac sodium, an antipyretic drug, did not affect this hyperthermia, indicating that the menthol-induced hyperthermia is not fever. Menthol application induced a rise in oxygen consumption, shivering-like muscle activity, tail skin vasoconstriction (autonomic responses), and heat-seeking behavior. All of them are typical heat-gain responses. These results support the hypothesis that TRPM8 mediates cooling-induced autonomic and behavioral heat-gain responses.

L-histidine is one of the essential amino acids for humans, and it plays a critical role as a component of proteins. L-histidine is also important as a precursor of histamine. Brain histamine is synthesized from L-histidine in the presence of histidine decarboxylase, which is expressed in histamine neurons. In the present study, we aimed to elucidate the importance of dietary L-histidine as a precursor of brain histamine and the histaminergic nervous system. C57BL/6J male mice at 8 wk of age were assigned to 2 different diets for at least 2 wk: the control (Con) diet (5.08 g L-histidine/kg diet) or the low L-histidine diet (LHD) (1.28 g L-histidine/kg diet). We measured the histamine concentration in the brain areas of Con diet-fed mice (Con group) and LHD-fed mice (LHD group). The histamine concentration was significantly lower in the LHD group [Con group vs. LHD group: histamine in cortex (means ± SEs): 13.9 ± 1.25 vs. 9.36 ± 0.549 ng/g tissue; P = 0.002]. Our in vivo microdialysis assays revealed that histamine release stimulated by high K(+) from the hypothalamus in the LHD group was 60% of that in the Con group (P = 0.012). However, the concentrations of other monoamines and their metabolites were not changed by the LHD. The open-field tests showed that the LHD group spent a shorter amount of time in the central zone (87.6 ± 14.1 vs. 50.0 ± 6.03 s/10 min; P = 0.019), and the light/dark box tests demonstrated that the LHD group spent a shorter amount of time in the light box (198 ± 8.19 vs. 162 ± 14.1 s/10 min; P = 0.048), suggesting that the LHD induced anxiety-like behaviors. However, locomotor activity, memory functions, and social interaction did not differ between the 2 groups. The results of the present study demonstrated that insufficient intake of histidine reduced the brain histamine content, leading to anxiety-like behaviors in the mice.

Appropriate regulation of inflammation during the perioperative period is important for achieving a stable postoperative course and early recovery and for reducing the malignancy relapse rate. For these reasons, an immune-modulating diet that includes anti-inflammatory substances such as ω-3 fatty acids has been used widely in clinical settings. The amino acids cystine and theanine are both involved in the synthesis of glutathione (GSH), a strong antioxidant, and there have been several reports that oral cystine and theanine enhance immunoreactions. This study was a pilot study to assess the effect of perioperatively administering oral cystine and theanine in gastric surgery patients and suggested that oral administration of these amino acids may reduce inflammation and promote recovery after gastric surgery. IntroductionPreventing organ dysfunction and immune suppression by inhibiting excess inflammation is considered an important aspect of perioperative surgical management, and several studies have indicated that immunonutrition is effective for this purpose.1,2 Administering the amino acids cystine and theanine has been shown to significantly suppress increases in C-reactive protein (CRP) levels and neutrophil counts and decreases in the number of lymphocytes after excessive exercise, resulting in a reduction in excessive inflammation and immune dysfunction; similar effects are expected to result from immunonutrition. 3 Cystine is a sulfur-containing amino acid that consists of 2 cysteine molecules joined by a disulfide bond. 4 Transporters on cell membranes (including those of neutrophils, macrophages, and dendritic cells) mediate the uptake of cystine into cells, and then thioredoxin rapidly 798P ENXXX10.1177/0148607112458798Journal of Parenteral and Enteral Nutrition / Vol. AbstractBackground: It has been reported that cystine and theanine, amino acids related to glutathione synthesis, have immunomodulatory effects, such as suppressing inflammation after strenuous exercise. In this study, we examined the effects of oral administration of cystine and theanine during the perioperative period as a pilot study. Methods: Forty-three cases of distal gastrectomy for cancer conducted in our department were assigned to the cystine and theanine group (CT group) or to the placebo control group (P group), and a randomized, singleblind, parallel-group study was then performed. Cystine (700 mg) and theanine (280 mg) or a placebo was administered to participants for 10 continuous days (4 days before to 5 days after surgery). Changes in pre-and postoperative interleukin (IL)-6, C-reactive protein (CRP), albumin, white blood cell (WBC) count, neutrophil count, total lymphocyte count, resting energy expenditure (REE), and body temperature were compared and examined. Results: Ten patients were excluded, leaving 33 patients in the study. The CT group had significantly lower IL-6 values (postoperative day [POD] 4), CRP levels (POD 7), neutrophil counts (POD 4), and body temperatures (POD 5) than the P group (P < .05). In addi...

Ingestion of CLA activates beta-oxidation and causes loss of body fat in rodents. We investigated the effects of dietary CLA on endurance capacity and energy metabolism during exercise in mice. Five-week-old male BALB/c mice were fed a control diet containing 1.0% linoleic acid or a diet containing 0.5% CLA that replaced an equivalent amount of linoleic acid for 1 wk. The maximum swimming time until fatigue was significantly higher in the CLA-fed group than in the control group. During treadmill running, the respiratory exchange ratio was significantly lower in the CLA-fed group, but oxygen consumption did not differ significantly between groups, suggesting that FA contributed more as an energy substrate in the CLA-fed mice. The muscle lipoprotein lipase activity was significantly higher in the CLA-fed group than in the control group. These results suggest that CLA ingestion increases endurance exercise capacity by promoting fat oxidation during exercise.