Involvement of SIK3 in Glucose and Lipid Homeostasis in Mice

Salt-inducible kinase 3 (SIK3), an AMP-activated protein kinase-related kinase, is induced in the murine liver after the consumption of a diet rich in fat, sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3−/− mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity) accompanied by cholestasis and cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be due to reduced energy storage, which is represented by the low expression levels of mRNA for components of the fatty acid synthesis pathways in the liver. The biliary disorders in Sik3−/− mice are associated with the dysregulation of gene expression programs that respond to nutritional stresses and are probably regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed at low levels in Sik3−/− mice. Lipid metabolism disorders in Sik3−/− mice are ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a novel energy regulator that modulates cholesterol and bile acid metabolism by coupling with retinoid metabolism, and may alter the size of energy storage in mice

Milk and dairy products: good or bad for human health? An assessment of the totality of scientific evidence

Background: There is scepticism about health effects of dairy products in the public, which is reflected in an increasing intake of plant-based drinks, for example, from soy, rice, almond, or oat. Objective: This review aimed to assess the scientific evidence mainly from meta-analyses of observational studies and randomised controlled trials, on dairy intake and risk of obesity, type 2 diabetes, cardiovascular disease, osteoporosis, cancer, and all-cause mortality. Results: The most recent evidence suggested that intake of milk and dairy products was associated with reduced risk of childhood obesity. In adults, intake of dairy products was shown to improve body composition and facilitate weight loss during energy restriction. In addition, intake of milk and dairy products was associated with a neutral or reduced risk of type 2 diabetes and a reduced risk of cardiovascular disease, particularly stroke. Furthermore, the evidence suggested a beneficial effect of milk and dairy intake on bone mineral density but no association with risk of bone fracture. Among cancers, milk and dairy intake was inversely associated with colorectal cancer, bladder cancer, gastric cancer, and breast cancer, and not associated with risk of pancreatic cancer, ovarian cancer, or lung cancer,while the evidence for prostate cancer risk was inconsistent.Finally,consumption of milk and dairy products was not associated with all-cause mortality. Calcium-fortified plant-based drinks have been included as an alternative to dairy products in the nutrition recommendations in several countries. However, nutritionally, cow’s milk and plant-based drinks are completely different foods,and an evidence-based conclusion on the health value of the plant-based drinks requires more studies in humans. Conclusion: The totality of available scientific evidence supports that intake of milk and dairy products contribute to meet nutrient recommendations, and may protect against the most prevalent chronic diseases, whereas very few adverse effects have been reported

Ussing Chamber

The Ussing chamber system is named after the Danish zoologist Hans Ussing, who invented the device in the 1950s to measure the short-circuit current as an indicator of net ion transport taking place across frog skin (Ussing and Zerahn, Acta Physiol Scand 23:110-127, 1951). Ussing chambers are increasingly being used to measure ion transport in native tissue, like gut mucosa, and in a monolayer of cells grown on permeable supports. However, the Ussing chamber system is, to date, not often applied for the investigation of the impact of food bioactives (proteins, sugars, lipids) on health. An Ussing system is generally comprised of a chamber and a perfusion system, and if needed, an amplifier and data acquisition system. The heart of the system lies in the chamber with the other components performing supporting roles. The classic chamber design is still in wide use today. However, several newer designs are now available that optimize for convenience and for diffusion- or electrophysiology-based measurements. A well designed Ussing chamber supports an epithelia membrane or cell monolayer in such a way that each side of the membrane is isolated and faces a separate chamber-half. The chambers are then filled with a physiologically relevant solution, such as Ringer’s solution. This configuration allows the researcher to make unique chemical and electrical adjustments to either side of the membrane with complete control. The Ussing chamber technique has its strengths and limitations, which will be explained in more detail in this chapter

Case report: lipid inclusion in glomerular endothelial and mesangial cells in a patient after contrast medium injection

Abstract Background It is well-recognized that injection of iodinated radiographic contrast media (CM) sometimes causes acute renal injury via multiple mechanisms, such as vasoconstriction, toxicity on glomerular endothelium and tubular epithelium and so forth. Case presentation A 51-year-old man developed acute renal injury with proteinuria after CM administration. To our surprise, in his renal biopsy sample the myelin figure like structure was observed in glomerular endothelium and mesangial cells by transmission electron microscopy. However the patient didn’t has any clinic clues of Fabry disease and other lysosomal storage disorders. Moreover in vitro cultured glomerular endothelial and mesangial cells we found CM triggers lipid aggregation along with the increased CD36 and decreased ABCA1 abundance. Thus this patient was administrated statin to correct the aberrant lipid trafficking, 2 months later at his next visit we found his renal function partially recovered with reduced proteinuria. Conclusions Besides the well-known underlying mechanisms, CM may cause renal impairment by triggering the dysregulated transportation of lipid. Furthermore statin is suggested to be a very promising medicine to decrease side effects of CM

Weight loss during cirrhosis is related to the etiology of liver disease

CONTEXT: Malnutrition is widely described in patients waiting for liver transplantation (LTx). However, risk factors associated with weight loss during liver disease have not yet been well studied. OBJECTIVES: The aim of this study was to assess weight loss and its risk factors during liver disease and up to the first appointment after transplantation. Patients who underwent LTx were retrospectively assessed for weight loss during liver disease while on the waiting list for LTx. The usual weight of the patients before disease and their weight on the first outpatient appointment after transplant were considered. Demographic, socioeconomic, lifestyle and clinical variables were collected to assess risk factors using a linear regression analysis. We retrospectively evaluated 163 patients undergoing LTx between 1997 and 2008. RESULTS: Patients lost in average 7.7 ± 12.4 kg while ill. Variables independently associated with weight loss by multiple linear regression analyses were as follows: former smoker (P = 0.03), greater body mass index (P<0.01), overweight before liver disease (P = 0.02) and indication for LTx (P = 0.01). Among these indications, patients with alcoholic cirrhosis had lost significantly more weight (P<0.01), and those with hepatitis C virus (P = 0.01) and autoimmune hepatitis (P = 0.02) had lost significantly less weight. CONCLUSIONS: Patients experienced weight loss during liver disease independent of age, sex, schooling and income; however, the etiology of liver disease was related to weight loss