Time-Lag Effect of Dietary Fiber and Fat Intake Ratio on Japanese Colon Cancer Mortality

The daily intake of total dietary fiber (TDF) was evaluated from data of the National Nutrition Survey (NNS) in Japan for 41 years since 1947. An interrelationship between the nutrient intake, including TDF, and the mortality from colon cancer in Japanese people was calculated by a simple correlation coefficient and time-series correlation coeffcient.TDF intake per capita decreased rapidly from 27.4 g in 1947 to 15.8 g in 1963, and subsequently decreased by a lesser rate to 15.3 g in 1987. Fat intake increased rapidly from 18.0 g in 1950 to 56.6 g in 1987.The age-adjusted mortality from colon cancer shows a significant positive correlation with both the intakes of animal protein and of total fat, and the fat energy ratio. A time-series analysis indicates that the mortality from colon cancer was negatively correlated with TDF with a 15-27 year delay, the maximum correlation existing with a 23-year lag (r = -0.947). The TDF intake was less than 17.9 g in 1965. At the same time, the mortality from colon cancer increased rapidly. A fat/TDF ratio above 3.0 resulted in a rapid increase in colon cancer mortality.The non-adjusted mortality from colon cancer has much the same interrelationship with TDF and fat intake as the adjusted figures. It is suggested that the cause of the increased mortality from colon cancer in Japan is positively related to the increased intake of fat and protein. In addition, the decrease in TDF intake has accelerated the mortality of colon cancer after a delay of 23-24 years. The importance of fat/TDF as a nutritional criterion for the incidence of colon cancer needs to be better recognized

Fatty acid intake in relation to reproductive hormones and testicular volume among young healthy men

Emerging evidence suggests that dietary fats may influence testicular function. However, most of the published literature on this field has used semen quality parameters as the only proxy for testicular function. We examined the association of fat intake with circulating reproductive hormone levels and testicular volume among healthy young Spanish men. This is a cross-sectional study among 209 healthy male volunteers conducted between October 2010 and November 2011 in Murcia Region of Spain. Participants completed questionnaires on lifestyle, diet, and smoking, and each underwent a physical examination, and provided a blood sample. Linear regression was used to examine the association between each fatty acid type and reproductive hormone levels and testicular volumes. Monounsaturated fatty acids intake was inversely associated with serum blood levels of calculated free testosterone, total testosterone, and inhibin B. A positive association was observed between the intake of polyunsaturated fatty acids, particularly of omega-6 polyunsaturated fatty acids, and luteinizing hormone concentrations. In addition, the intake of trans fatty acids was associated with lower total testosterone and calculated free testosterone concentrations （Ptrend = 0.01 and 0.02, respectively）. The intake of omega-3 polyunsaturated fatty acids was positively related to testicular volume while the intake of omega-6 polyunsaturated fatty acids and trans fatty acids was inversely related to testicular volume. These data suggest that fat intake, and particularly intake of omega 3, omega 6, and trans fatty acids, may influence testicular function.

Ablation of Akt2 and AMPKα2 rescues high fat diet-induced obesity and hepatic steatosis through Parkin-mediated mitophagy

Given the opposing effects of Akt and AMP-activated protein kinase(AMPK)on metabolic homeostasis,this study examined the effects of deletion of Akt2 and AMPKα2 on fat diet-induced hepatic steatosis.Akt2–Ampkα2 double knockout(DKO)mice were placed on high fat diet for 5 months.Glucose metabolism,energy homeostasis,cardiac function,lipid accumulation,and hepatic steatosis were examined.DKO mice were lean without anthropometric defects.High fat intake led to adiposity and decreased respiratory exchange ratio(RER)in wild-type(WT)mice,which were ablated in DKO but not Akt2^(-/-) and Ampkα2^(-/-) mice.High fat intake increased blood and hepatic triglycerides and cholesterol,promoted hepatic steatosis and injury in WT mice.These effects were eliminated in DKO but not Akt2^(-/-) and Ampkα2^(-/-) mice.Fat diet promoted fat accumulation,and enlarged adipocyte size,the effect was negated in DKO mice.Fat intake elevated fatty acid synthase(FAS),carbohydrate-responsive element-binding protein(CHREBP),sterol regulatory element-binding protein 1(SREBP1),peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),peroxisome proliferator-activated receptor-α(PPARα),PPARγ,stearoyl-CoA desaturase 1(SCD-1),phosphoenolpyruvate carboxykinase(PEPCK),glucose 6-phosphatase(G6Pase),and diglyceride O-acyltransferase 1(DGAT1),the effect was absent in DKO but not Akt2^(-/-) and Ampkα2^(-/-) mice.Fat diet dampened mitophagy,promoted inflammation and phosphorylation of forkhead box protein O1(FoxO1)and AMPKα1(Ser^(485)),the effects were eradicated by DKO.Deletion of Parkin effectively nullified DKO-induced metabolic benefits against high fat intake.Liver samples from obese humans displayed lowered microtubule-associated proteins 1A/1B light chain 3B(LC3B),Pink1,Parkin,as well as enhanced phosphorylation of Akt,AMPK(Ser^(485)),and FoxO1,which were consolidated by RNA sequencing(RNAseq)and mass spectrometry analyses from rodent and human livers.These data suggest that concurrent deletion of Akt2 and AMPKα2 offers resilience to fat diet-induced obesity and hepatic steatosis,possibly through preservation of Parkin-mediated mitophagy and lipid metabolism.