Wheat alkylresorcinol increases fecal lipid excretion and suppresses feed efficiency in mice depending on time of supplementation.

OBJECTIVE: The regular consumption of whole grains is linked to a lower likelihood of developing metabolic disorders. We previously found that chronic supplementation with wheat alkylresorcinols (ARs) prevents obesity and its associated metabolic symptoms induced by a high-fat high-sucrose diet (HFHSD) in mice. The aim of this study was to examine the time-of-day-dependence of these effects in mice. METHODS: Eight-wk-old male C57 BL/6 J mice were individually housed under a 12-h light/dark cycle (Zeitgeber time; ZT0, lights on; ZT12, lights off) and given access to a HFHSD from ZT12-16 (activity onset) and ZT20-24 (activity offset) to respectively represent breakfast and dinner times for 3 wk. Thereafter, the HFHSD was replaced with the same diet containing 0.4% ARs at either ZT12-16 or ZT20-24 for 8 wk. Control mice received the HFHSD without ARs at both feeding times. RESULTS: Supplementation with ARs significantly suppressed feed efficiency when given at breakfast, but not at dinner. ARs consumed at breakfast increased fecal lipid content and decreased the expression of Fat/Cd36 in enterocytes that enhances lipid uptake, but did not affect hepatic and blood lipid levels. The consumption of ARs at breakfast also upregulated the expression of Irs1, a key gene for insulin signaling in white adipose tissue and attenuated elevated blood leptin levels induced by the diet. This led to high scores for the homeostasis model assessment of insulin sensitivity, and the adiponectin/leptin ratio, a negative index of adipose tissue dysfunction. CONCLUSIONS: These findings suggested that ARs ameliorate feed efficiency by decreasing dietary lipid absorption more effectively at the time of activity onset than offset. Further studies are needed to elucidate the molecular mechanism of the time-of-day-dependent effects of ARs on diet-induced metabolic disorders.

Acute Effects of Transdermal Administration of Jojoba Oil on Lipid Metabolism in Mice.

Background and objectives: Aroma therapy is a complementary therapy using essential oils diluted with carrier oils. Jojoba oils have been widely used as carrier oils. However, limited information is available regarding their effects on blood biochemical parameters. This study aimed to investigate the effect of transdermal administration of jojoba oil on blood biochemical parameters in mice. Materials and Methods: Eight-week-old male hairless mice were randomly divided into naïve control and treatment groups. In the treatment group, mice were topically administered 4 µL of jojoba oil, per gram of body weight, on the dorsa 30 min before euthanasia. Thereafter, serum biochemical parameters were assayed, and gene expression was analyzed in various tissues via a real-time polymerase chain reaction. Results: Serum non-esterified fatty acid (NEFA) levels increased significantly 30 min after topical application of jojoba oil (p < 0.05). Atgl was significantly upregulated in the liver (p < 0.05), and Atgl upregulation in the liver was positively correlated with serum NEFA levels (r = 0.592, p < 0.05). Furthermore, a trend of decreasing fatty acid trafficking-related gene (FABPpm, FATP-1, FATP-3, and FATP-4) expression in the skin after topical application of jojoba oil (p = 0.067, 0.074, 0.076, and 0.082, respectively) was observed. Conclusions: Serum NEFA levels were elevated 30 min after transdermal administration of jojoba oil. The mechanisms of elevated serum NEFA levels might be related to both enhanced lipolysis in the liver and reduced fatty acid trafficking in the skin.

Wheat alkylresorcinols reduce micellar solubility of cholesterol in vitro and increase cholesterol excretion in mice.

Epidemiological studies have shown that the consumption of whole grains can reduce risk for metabolic disorders. We recently showed that chronic supplementation with wheat alkylresorcinols (ARs) prevents glucose intolerance and insulin resistance with hepatic lipid accumulation induced in mice by a high-fat high-sucrose diet (HFHSD). This study examines the effects of ARs on the micellar solubility of cholesterol in vitro, as well as the effects of transient AR supplementation on faecal lipid excretion and plasma lipid levels in mice. We found that ARs formed bile micelles with taurocholate independently of phospholipids, and dose-dependently decreased the micellar solubility of cholesterol in a biliary micelle model. Transient AR supplementation with HFHSD increased faecal cholesterol and triglyceride contents and decreased plasma cholesterol concentrations. These suggest that one underlying mechanism through which ARs suppress diet-induced obesity is by interfering with the micellar cholesterol solubilisation in the digestive tract, which subsequently decreases cholesterol absorption.

Efficacy of Kaempferia parviflora in a mouse model of obesity-induced dermatopathy.

Obesity results from excessive energy intake and physical inactivity, and predisposes one to various diseases. One of these reasons is that enlargement of adipocytes raises the lipid metabolic abnormalities that affect various organs. The skin is one such organ, and it has been reported that subcutaneous adipocyte cells secrete various factors and these factors are involved in reduction of dermal collagen fibers and fragility of the skin in obesity. The present study explored the efficacy of Kaempferia parviflora (KP) in preventing obesity-induced dermatopathy. We used Tsumura Suzuki obese diabetes (TSOD) mice as an obesity model. TSOD mice were fed a standard diet (MF) mixed with either an ethanol extract from KP (KPE), polymethoxyflavonoid-rich extract from KP (PMF), or polymethoxyflavonoid-poor extract from KP (X). We then evaluated the effect of these three KP fractions on aging-like skin damage induced by UVB irradiation. KPE and PMF caused a significant decrease of mouse body weight, and suppressed the increase in the thickness of the subcutaneous fat layer. In addition, KPE shifted the frequency of subcutaneous adipocyte sizes towards smaller cells possibly via its polypharmacological actions. Scanning electron microscopy revealed that the stereostructure of the collagenous fibers in the dermis was better retained in the KPE and PMF groups, in that order. These results offer the first evidence that KPE can attenuate obesity-induced dermatopathy more effectively than PMF, suggesting that KPE (or KP) might be a candidate supplement for preventing obesity-related skin disorders.

Attenuated food anticipatory activity and abnormal circadian locomotor rhythms in Rgs16 knockdown mice.

Regulators of G protein signaling (RGS) are a multi-functional protein family, which functions in part as GTPase-activating proteins (GAPs) of G protein α-subunits to terminate G protein signaling. Previous studies have demonstrated that the Rgs16 transcripts exhibit robust circadian rhythms both in the suprachiasmatic nucleus (SCN), the master circadian light-entrainable oscillator (LEO) of the hypothalamus, and in the liver. To investigate the role of RGS16 in the circadian clock in vivo, we generated two independent transgenic mouse lines using lentiviral vectors expressing short hairpin RNA (shRNA) targeting the Rgs16 mRNA. The knockdown mice demonstrated significantly shorter free-running period of locomotor activity rhythms and reduced total activity as compared to the wild-type siblings. In addition, when feeding was restricted during the daytime, food-entrainable oscillator (FEO)-driven elevated food-anticipatory activity (FAA) observed prior to the scheduled feeding time was significantly attenuated in the knockdown mice. Whereas the restricted feeding phase-advanced the rhythmic expression of the Per2 clock gene in liver and thalamus in the wild-type animals, the above phase shift was not observed in the knockdown mice. This is the first in vivo demonstration that a common regulator of G protein signaling is involved in the two separate, but interactive circadian timing systems, LEO and FEO. The present study also suggests that liver and/or thalamus regulate the food-entrained circadian behavior through G protein-mediated signal transduction pathway(s).