Cabergoline counteracts adipose and skeletal muscle lipid accumulation: A novel therapeutic approach to obesity?

Objective: Obesity represents a global health problem with large costs for public health. Cabergoline (CAB), a potent dopamine agonist with a high affinity for type 2 dopamine receptor (D2R), usually used in clinical practice for hyperprolactinemia management, has been reported to significantly decrease metabolic syndrome prevalence and visceral adiposity associated with improved insulin sensitivity in prolactinoma patients. Nevertheless, scant data are reported about CAB effects on obesity condition.

DSM 17938 reverses gut metabolic dysfunction induced by Western diet in adult rats.

Introduction: Microencapsulation of probiotic bacteria is an efficient and innovative new technique aimed at preserving bacterial survival in the hostile conditions of the gastrointestinal tract. However, understanding whether a microcapsule preserves the effectiveness of the bacterium contained within it is of fundamental importance.

Methods: Male Wistar rats aged 90 days were fed a control diet or a Western diet for 8 weeks, with rats fed the Western diet divided into three groups: one receiving the diet only (W), the second group receiving the Western diet and free DSM 17938 (WR), and the third group receiving the Western diet and microencapsulated DSM 17938 (WRM).

Age-Dependent Skeletal Muscle Mitochondrial Response to Short-Term Increased Dietary Fructose.

The harmful effect of a long-term high-fructose diet is well established, but the age-dependent physiological responses that can be triggered by a short-term high-fructose diet in skeletal muscles have not been deeply explored. Therefore, the aim of this work was to compare the alterations in mitochondrial energetic and insulin responsiveness in the skeletal muscle induced by a short-term (2 weeks) fructose feeding in rats of different ages. For this purpose, fructose and uric acid levels, insulin sensitivity, mitochondrial bioenergetics and oxidative status were evaluated in the skeletal muscles from young (30 days old) and adult (90 days old) rats.

Skeletal muscle insulin resistance and adipose tissue hypertrophy persist beyond the reshaping of gut microbiota in young rats fed a fructose-rich diet.

To investigate whether short term fructose-rich diet induces changes in the gut microbiota as well as in skeletal muscle and adipose tissue physiology and verify whether they persist even after fructose withdrawal, young rats of 30 d of age were fed for 3 weeks a fructose-rich or control diet. At the end of the 3-weeks period, half of the rats from each group were maintained for further 3 weeks on a control diet. Metagenomic analysis of gut microbiota and short chain fatty acids levels (faeces and plasma) were investigated.

Gut and liver metabolic responses to dietary fructose - are they reversible or persistent after switching to a healthy diet?

The link between increased fructose intake and induction of gut and liver dysfunction has been established, while it remains to be understood whether this damage is reversible, particularly in the young population, in which the intake of fructose has reached dramatic levels. To this end, young (30 days old) rats were fed a fructose-rich or control diet for 3 weeks to highlight the early response of the gut and liver to increased fructose intake. After this period, fructose-fed rats were returned to a control diet for 3 weeks and compared to the rats that received the control diet for the entire period to identify whether fructose-induced changes in the gut-liver axis persist or not after switching back to a control diet.

Prolonged Changes in Hepatic Mitochondrial Activity and Insulin Sensitivity by High Fructose Intake in Adolescent Rats.

Persistence of damage induced by unhealthy diets during youth has been little addressed. Therefore, we investigated the impact of a short-term fructose-rich diet on liver metabolic activity in adolescent rats and the putative persistence of alterations after removing fructose from the diet. Adolescent rats were fed a fructose-rich diet for three weeks and then switched to a control diet for further three weeks.

A Short-Term Western Diet Impairs Cholesterol Homeostasis and Key Players of Beta Amyloid Metabolism in Brain of Middle Aged Rats.

Scope: Cholesterol homeostasis is crucial for brain functioning. Unhealthy nutrition can influence cerebral physiology, but the effect of western diets on brain cholesterol homeostasis, particularly at middle age, is unknown. Given the link between brain cholesterol alteration and beta amyloid production, the aim is to evaluate whether a diet rich in fat and fructose affects the protein network implicated in cholesterol synthesis and shuttling between glial cells and neurons, as well as crucial markers of beta amyloid metabolism.

Adipose Tissue and Brain Metabolic Responses to Western Diet-Is There a Similarity between the Two?

Dietary fats and sugars were identified as risk factors for overweight and neurodegeneration, especially in middle-age, an earlier stage of the aging process. Therefore, our aim was to study the metabolic response of both white adipose tissue and brain in middle aged rats fed a typical Western diet (high in saturated fats and fructose, HFF) and verify whether a similarity exists between the two tissues. Specific cyto/adipokines (tumor necrosis factor alpha (TNF-α), adiponectin), critical obesity-inflammatory markers (haptoglobin, lipocalin), and insulin signaling or survival protein network (insulin receptor substrate 1 (IRS), Akt, Erk) were quantified in epididymal white adipose tissue (e-WAT), hippocampus, and frontal cortex.

Early Hepatic Oxidative Stress and Mitochondrial Changes Following Western Diet in Middle Aged Rats.

To assess the effect of 4 weeks of high fat-high fructose feeding on whole body composition, energy balance, specific markers of oxidative stress and inflammation, and insulin sensitivity in the liver of middle-aged rats, rats (1 year) were fed a diet rich in saturated fatty acids and fructose (HFF rats), mimicking the "Western diet", and compared with rats of the same age that were fed a low fat diet (LF rats). HFF rats exhibited a significant increase in the gain of body weight, energy, and lipids compared to LF rats. HFF rats also showed hepatic insulin resistance, together with an increase in plasma triglycerides, cholesterol, and tumor necrosis factor alpha.

Metabolic Effects of the Sweet Protein MNEI as a Sweetener in Drinking Water. A Pilot Study of a High Fat Dietary Regimen in a Rodent Model.

Sweeteners have become integrating components of the typical western diet, in response to the spreading of sugar-related pathologies (diabetes, obesity and metabolic syndrome) that have stemmed from the adoption of unbalanced dietary habits. Sweet proteins are a relatively unstudied class of sweet compounds that could serve as innovative sweeteners, but their introduction on the food market has been delayed by some factors, among which is the lack of thorough metabolic and toxicological studies. We have tried to shed light on the potential of a sweet protein, MNEI, as a fructose substitute in beverages in a typical western diet, by studying the metabolic consequences of its consumption on a Wistar rat model of high fat diet-induced obesity.

Bacillus megaterium SF185 spores exert protective effects against oxidative stress in vivo and in vitro.

Endogenous reactive oxygen species (ROS) are by-products of the aerobic metabolism of cells and have an important signalling role as secondary messengers in various physiological processes, including cell growth and development. However, the excessive production of ROS, as well as the exposure to exogenous ROS, can cause protein oxidation, lipid peroxidation and DNA damages leading to cell injuries. ROS accumulation has been associated to the development of health disorders such as neurodegenerative and cardiovascular diseases, inflammatory bowel disease and cancer.

Effect of Initial Aging and High-Fat/High-Fructose Diet on Mitochondrial Bioenergetics and Oxidative Status in Rat Brain.

Middle age is an early stage of the aging process, during which the consumption of diets rich in saturated fats and/or simple sugars might influence brain function, but only few data are available on this issue. We therefore investigated the impact of a diet rich in saturated fat and fructose (HFF) on mitochondrial physiology in hippocampus and frontal cortex of middle-aged rats (1 year old), by including a group of adult rats (90 days) as a "negative control," lacking the putative effect of aging. Middle-aged rats were fed HFF or control diet for 4 weeks.

Brain Nrf2 pathway, autophagy, and synaptic function proteins are modulated by a short-term fructose feeding in young and adult rats.

A strong rise of the fructose content in the human diet occurred in the last decade, as corn syrup is widely used as a sweetener for beverages and processed food. Since young people make a widespread consumption of added sugars, we evaluated the effects of a two weeks fructose-rich diet on brain redox homeostasis, autophagy and synaptic plasticity in the cortex of young and adults rats, in order to highlight the early risks to which brain is exposed. Short-term fructose feeding was associated with an imbalance of redox homeostasis, as lower amount of Nuclear factor (erythroid derived 2)-like 2, lower activity of Glucose 6-phosphate dehydrogenase and Glutathione reductase, together with lower Glutathione/Oxidized Glutathione ratio, were found in fructose-fed young and adult rats.

Early Effects of a Low Fat, Fructose-Rich Diet on Liver Metabolism, Insulin Signaling, and Oxidative Stress in Young and Adult Rats.

The increase in the use of refined food, which is rich in fructose, is of particular concern in children and adolescents, since the total caloric intake and the prevalence of metabolic syndrome are increasing continuously in these populations. Nevertheless, the effects of high fructose diet have been mostly investigated in adults, by focusing on the effect of a long-term fructose intake. Notably, some reports evidenced that even short-term fructose intake exerts detrimental effects on metabolism.

Dietary fructose causes defective insulin signalling and ceramide accumulation in the liver that can be reversed by gut microbiota modulation.

: The link between metabolic derangement of the gut-2013liver-visceral white adipose tissue (v-WAT) axis and gut microbiota was investigated. : Rats were fed a fructose-rich diet and treated with an antibiotic mix. Inflammation was measured in portal plasma, ileum, liver, and v-WAT, while insulin signalling was analysed by measuring levels of phosphorylated kinase Akt.

Short-Term Fructose Feeding Induces Inflammation and Oxidative Stress in the Hippocampus of Young and Adult Rats.

The drastic increase in the consumption of fructose encouraged the research to focus on its effects on brain physio-pathology. Although young and adults differ largely by their metabolic and physiological profiles, most of the previous studies investigated brain disturbances induced by long-term fructose feeding in adults. Therefore, we investigated whether a short-term consumption of fructose (2 weeks) produces early increase in specific markers of inflammation and oxidative stress in the hippocampus of young and adult rats.

Polyunsaturated Fatty Acids Stimulate Lipogenesis and Improve Glucose Homeostasis during Refeeding with High Fat Diet.

The recovery of body weight after a period of caloric restriction is accompanied by an enhanced efficiency of fat deposition and hyperinsulinemia-which are exacerbated by isocaloric refeeding on a high fat diet rich in saturated and monounsaturated fatty acids (SFA-MUFA), and poor in polyunsaturated fatty acids (PUFA), and associated with a blunting of lipogenesis in adipose tissue and liver. As high fat diets rich in PUFA have been shown to limit the excess fat deposition and improve glucose homeostasis, we investigated here the extent to which lipogenesis in liver and adipose tissues (white and brown), as well as hepatic oxidative stress, are influenced by refeeding on diets rich in PUFA. In rats calorically restricted for 14 days and refed for 14 days on isocaloric amounts of a high fat diet rich in lard (i.

Fructose-Rich Diet Affects Mitochondrial DNA Damage and Repair in Rats.

Evidence indicates that many forms of fructose-induced metabolic disturbance are associated with oxidative stress and mitochondrial dysfunction. Mitochondria are prominent targets of oxidative damage; however, it is not clear whether mitochondrial DNA (mtDNA) damage and/or its lack of repair are events involved in metabolic disease resulting from a fructose-rich diet. In the present study, we evaluated the degree of oxidative damage to liver mtDNA and its repair, in addition to the state of oxidative stress and antioxidant defense in the liver of rats fed a high-fructose diet.

Fat Quality Influences the Obesogenic Effect of High Fat Diets.

High fat and/or carbohydrate intake are associated with an elevated risk for obesity and chronic diseases such as diabetes and cardiovascular diseases. The harmful effects of a high fat diet could be different, depending on dietary fat quality. In fact, high fat diets rich in unsaturated fatty acids are considered less deleterious for human health than those rich in saturated fat.

A possible link between hepatic mitochondrial dysfunction and diet-induced insulin resistance.

Background: Mitochondria are the main cellular sites devoted to ATP production and lipid oxidation. Therefore, the mitochondrial dysfunction could be an important determinant of cellular fate of circulating lipids, that accumulate in the cytoplasm, if they are not oxidized. The ectopic fat accumulation is associated with the development of insulin resistance, and a link between mitochondrial dysfunction and insulin resistance has been proposed.

Rescue of Fructose-Induced Metabolic Syndrome by Antibiotics or Faecal Transplantation in a Rat Model of Obesity.

A fructose-rich diet can induce metabolic syndrome, a combination of health disorders that increases the risk of diabetes and cardiovascular diseases. Diet is also known to alter the microbial composition of the gut, although it is not clear whether such alteration contributes to the development of metabolic syndrome. The aim of this work was to assess the possible link between the gut microbiota and the development of diet-induced metabolic syndrome in a rat model of obesity.

Skeletal muscle mitochondrial energetic efficiency and aging.

Aging is associated with a progressive loss of maximal cell functionality, and mitochondria are considered a key factor in aging process, since they determine the ATP availability in the cells. Mitochondrial performance during aging in skeletal muscle is reported to be either decreased or unchanged. This heterogeneity of results could partly be due to the method used to assess mitochondrial performance.

Mitochondrial efficiency and insulin resistance.

Insulin resistance, "a relative impairment in the ability of insulin to exert its effects on glucose, protein and lipid metabolism in target tissues," has many detrimental effects on metabolism and is strongly correlated to deposition of lipids in non-adipose tissues. Mitochondria are the main cellular sites devoted to ATP production and fatty acid oxidation. Therefore, a role for mitochondrial dysfunction in the onset of skeletal muscle insulin resistance has been proposed and many studies have dealt with possible alteration in mitochondrial function in obesity and diabetes, both in humans and animal models.

Fructose supplementation worsens the deleterious effects of short-term high-fat feeding on hepatic steatosis and lipid metabolism in adult rats.

The purpose of the present study was to examine the short-term effect of high-fat or high-fat-high-fructose feeding on hepatic lipid metabolism and mitochondrial function in adult sedentary rats. Adult male rats were fed a high-fat or high-fat-high-fructose diet for 2 weeks. Body and liver composition, hepatic steatosis, plasma lipid profile and hepatic insulin sensitivity, together with whole-body and hepatic de novo lipogenesis, were assessed.

Alterations in proton leak, oxidative status and uncoupling protein 3 content in skeletal muscle subsarcolemmal and intermyofibrillar mitochondria in old rats.

Background: We considered of interest to evaluate how aging affects mitochondrial function in skeletal muscle.

Methods: We measured mitochondrial oxidative capacity and proton leak, together with lipid oxidative damage, superoxide dismutase specific activity and uncoupling protein 3 content, in subsarcolemmal and intermyofibrillar mitochondria from adult (six months) and old (two years) rats. Body composition, resting metabolic rate and plasma non esterified fatty acid levels were also assessed.