Preserving of postnatal leptin signaling in obesity-resistant lou/c rats following a perinatal high-fat diet

Physiological processes at adulthood, such as energy metabolism and insulin sensitivity may originate before or weeks after birth. These underlie the concept of fetal and/or neonatal programming of adult diseases, which is particularly relevant in the case of obesity and type 2 diabetes. The aim of this study was to determine the impact of a perinatal high fat diet on energy metabolism and on leptin as well as insulin sensitivity, early in life and at adulthood in two strains of rats presenting different susceptibilities to diet-induced obesity. The impact of a perinatal high fat diet on glucose tolerance and diet-induced obesity was also assessed. The development of glucose intolerance and of increased fat mass was confirmed in the obesity-prone Wistar rat, even after 28 days of age. By contrast, in obesity-resistant Lou/C rats, an improved early leptin signaling may be responsible for the lack of deleterious effect of the perinatal high fat diet on glucose tolerance and increased adiposity in response to high fat diet at adulthood. Altogether, this study shows that, even if during the perinatal period adaptation to the environment appears to be genetically determined, adaptive mechanisms to nutritional challenges occurring at adulthood can still be observed in rodents

Mechanisms involved in impaired glucose transport in adult rat cardiomyocytes

One of the central features of the metabolic syndrome is insulin resistance which is described as the inability of insulin to stimulate glucose uptake. This disorder has been intensively investigated in adipocytes and skeletal muscles. Insulin resistance also affects the myocardium however the involved mechanisms remain elusive. Therefore, we aimed to investigate the cellular mechanisms contributing to impaired glucose metabolism in cultured adult rat cardiomyocytes (ARC). Firstly, we demonstrated that ERK1/2 activation prevents the formation of the microtubule organizing center and disrupts microtubule architecture leading to altered stimulated-glucose transport in ARC. Secondly, we found that exposure of cardiomyocytes to fatty acids and peroxisome proliferator activated receptors agonist was accompanied by impaired stimulated glucose transport. Thirdly, we showed that cardiotrophin-1 is involved in regulation of myocardial glucose metabolism in a dose dependant manner. In summary, this thesis provides new insights into the mechanisms regulating glucose metabolism in cardiomyocytes

Impact of SGLT Inhibitors on Multiple Organ Defects in Diabetes

Introduction: Diabetes leads to multiple organ defects and cellular dysfunctions such as increased expression of sodium-glucose like transporters (SGLTs). These transporters contribute to glucose homeostasis through glucose reabsorption in the proximal renal tubule. When inhibited, it results in reduced hyperglycemia, increased glucosuria and decreased HbA1c.Aims: This review article summarizes the positive and adverse effects of the three main SGLT inhibitors used in Europe, on different organs with the aim of providing useful information to clinicians in order to select the adapted SGLT inhibitor in regard to patient health problems.Discussion: Recently, SGLT pharmacological inhibitors have been developed to manage hyperglycemia in diabetic patients. SGLT inhibitors like canagliflozin, dapagliflozin, empagliflozin were approved by the Food and Drug Administration (FDA) in 2013 for use in Europe. Beyond their impact on glucose re-uptake by the kidney, these inhibitors exert beneficial pleiotropic effects. Nevertheless, several studies have recently warned the scientific community regarding adverse effects of these agents. Therefore, clinicians should consider these effects to adapt the treatment regarding patients' health.Conclusion: The use of SGLT inhibitor in the treatment of type 2 diabetes should be considered with the perspective of general health state of the patient. In fact, SGLT inhibitors promote pleiotropic effects, among which some are beneficial for certain organs while some are deleterious.</p

Diets and nonalcoholic fatty liver disease: The good and the bad

Nonalcoholic fatty liver disease (NAFLD) is now described as the hepatic manifestation of the metabolic syndrome and is the most frequent chronic liver disease, affecting about one out of three people in the western world. NAFLD is strongly linked to insulin resistance, which represents a key risk factor for the development of type 2 diabetes. To date, there are no reliable and efficient pharmacotherapies in the treatment of NAFLD. However, obesity, which represents one of the main features of the metabolic syndrome, is strongly associated with NAFLD. Therefore, lifestyle modifications, i.e. weight loss and increased physical activity, are the very first clinical approaches aiming at treating NAFLD. However, although weight loss is beneficial in NAFLD, certain diets known to induce weight loss can actually cause or exacerbate this disease, and therefore induce insulin resistance, such as very low carbohydrate, high fat diets. Moreover, macronutrient diet composition can impact NAFLD without any change in body weight. Indeed, diets rich in fatty acids, particularly saturated, or in refined carbohydrates such as those found in soft drinks, can actually exacerbate NAFLD. The aim of this review is to discuss the role of weight loss and macronutrients modifications, particularly the role of fat and carbohydrate diet composition, in the treatment of NAFLD

Emerging role of epigenetics and miRNA in diabetic cardiomyopathy

The prevalence of heart failure independent of coronary artery disease and hypertension is increasing rapidly in diabetic patients. Thus, this pathophysiology has been recognized as a distinct clinical entity termed "diabetic cardiomyopathy." Several studies support the notion that diabetes is a threatening insult for the myocardium resulting in functional, cellular, and structural changes manifesting as a cardiac myopathy. Recent data suggested that epigenetics including DNA and histone modifications as well as microRNAs play an important role in the development of cardiac diseases. The role of epigenetics in diabetes is largely recognized; however, its role in diabetes-associated cardiomyopathy remains elusive. Thus, molecular, cellular, and functional modulations in the diabetic cardiomyopathy will be investigated in this review. Moreover, particular attention will be drawn on the epigenetic mechanisms that may play an important role in the pathophysiology of diabetic cardiomyopathy

Alpha-fetoprotein: a controversial prognostic biomarker for small hepatocellular carcinoma

The assessment of the prognosis in patients with early hepatocellular carcinoma represents a hot-topic issue that requires further improvements and clarifications. The life expectancy of the patients has been shown to depend on several clinical and histological parameters (such as patient's general conditions, macroscopic tumor morphology and histopathology). Recently, the prognostic role of some biomarkers [i.e., alpha-fetoprotein (AFP)] has been also investigated with controversial findings mainly on the assessment of patient survival. The study by Giannini et al failed to show a prognostic value of AFP on survival of patients with well-compensated cirrhosis and small hepatocellular carcinoma. Since the study presents some limitations, a larger clinical trial is needed to clarify the potential prognostic role of serum AFP levels in these patients