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Adipose tissue insulin resistance and lipidome alterations as the characterizing factors of non-alcoholic steatohepatitis.
Guerra, S, Mocciaro, G, Gastaldelli, A
European journal of clinical investigation. 2022;(3):e13695
Abstract
BACKGROUND The prevalence of non-alcoholic fatty liver disease (NAFLD) is now 25% in the general population but increases to more than 55% in subjects with obesity and/or type 2 diabetes. Simple steatosis (NAFL) can develop into more severe forms, that is non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma leading to death. METHODS In this narrative review, we have discussed the current knowledge in the pathophysiology of fatty liver disease, including both metabolic and non-metabolic factors, insulin resistance, mitochondrial function, as well as the markers of liver damage, giving attention to the alterations in lipid metabolism and production of lipotoxic lipids. RESULTS Insulin resistance, particularly in the adipose tissue, is the main driver of NAFLD due to the excess release of fatty acids. Lipidome analyses have shown that several lipids, including DAGs and ceramides, and especially if they contain saturated lipids, act as bioactive compounds, toxic to the cells. Lipids can also affect mitochondrial function. Not only lipids, but also amino acid metabolism is impaired in NAFL/NASH, and some amino acids, as branched-chain and aromatic amino acids, glutamate, serine and glycine, have been linked to impaired metabolism, insulin resistance and severity of NAFLD and serine is a precursor of ceramides. CONCLUSIONS The measurement of lipotoxic species and adipose tissue dysfunction can help to identify individuals at risk of progression to NASH.
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2.
Achieving an Optimal Fat Loss Phase in Resistance-Trained Athletes: A Narrative Review.
Ruiz-Castellano, C, Espinar, S, Contreras, C, Mata, F, Aragon, AA, Martínez-Sanz, JM
Nutrients. 2021;(9)
Abstract
Managing the body composition of athletes is a common practice in the field of sports nutrition. The loss of body weight (BW) in resistance-trained athletes is mainly conducted for aesthetic reasons (bodybuilding) or performance (powerlifting or weightlifting). The aim of this review is to provide dietary-nutritional strategies for the loss of fat mass in resistance-trained athletes. During the weight loss phase, the goal is to reduce the fat mass by maximizing the retention of fat-free mass. In this narrative review, the scientific literature is evaluated, and dietary-nutritional and supplementation recommendations for the weight loss phase of resistance-trained athletes are provided. Caloric intake should be set based on a target BW loss of 0.5-1.0%/week to maximize fat-free mass retention. Protein intake (2.2-3.0 g/kgBW/day) should be distributed throughout the day (3-6 meals), ensuring in each meal an adequate amount of protein (0.40-0.55 g/kgBW/meal) and including a meal within 2-3 h before and after training. Carbohydrate intake should be adapted to the level of activity of the athlete in order to training performance (2-5 g/kgBW/day). Caffeine (3-6 mg/kgBW/day) and creatine monohydrate (3-5 g/day) could be incorporated into the athlete's diet due to their ergogenic effects in relation to resistance training. The intake of micronutrients complexes should be limited to special situations in which there is a real deficiency, and the athlete cannot consume through their diet.
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3.
Pathophysiology of Obesity.
Kessler, C
The Nursing clinics of North America. 2021;(4):465-478
Abstract
As obesity continues a relentless march across the globe, researchers are beginning to unlock the complicated interplay among obesity, its ensuing inflammation, and downstream complications. It is becoming clear that obesity is a chronic, multifactorial, inflammatory disease of maladaptive adipose tissue mass involving complex links among genetics, hormonal-signaling, and the environment. Understanding the intricate pathogenesis of obesity and its sequela will go a long way to discovering better treatment options and lessen anti-obesity bias.
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4.
Plasticity and heterogeneity of thermogenic adipose tissue.
Sun, W, Modica, S, Dong, H, Wolfrum, C
Nature metabolism. 2021;(6):751-761
Abstract
The perception of adipose tissue, both in the scientific community and in the general population, has changed dramatically in the past 20 years. While adipose tissue was thought for a long time to be a rather simple lipid storage entity, it is now recognized as a highly heterogeneous organ and a critical regulator of systemic metabolism, composed of many different subtypes of cells, with important endocrine functions. Additionally, adipose tissue is nowadays recognized to contribute to energy turnover, due to the presence of specialized thermogenic adipocytes, which can be found in many adipose depots. This review discusses the unprecedented insights that we have gained into the heterogeneity of thermogenic adipocytes and their respective precursors due to the technical developments in single-cell and nucleus technologies. These methodological advances have increased our understanding of how adipose tissue catabolic function is influenced by developmental and intercellular communication events.
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5.
Recent Advances in Adipose Tissue Dysfunction and Its Role in the Pathogenesis of Non-Alcoholic Fatty Liver Disease.
Wang, X, Rao, H, Liu, F, Wei, L, Li, H, Wu, C
Cells. 2021;(12)
Abstract
Obesity is a serious ongoing health problem that significantly increases the incidence of nonalcoholic fatty liver disease (NAFLD). During obesity, adipose tissue dysfunction is obvious and characterized by increased fat deposition (adiposity) and chronic low-grade inflammation. The latter has been implicated to critically promote the development and progression of NAFLD, whose advanced form non-alcoholic steatohepatitis (NASH) is considered one of the most common causes of terminal liver diseases. This review summarizes the current knowledge on obesity-related adipose dysfunction and its roles in the pathogenesis of hepatic steatosis and inflammation, as well as liver fibrosis. A better understanding of the crosstalk between adipose tissue and liver under obesity is essential for the development of new and improved preventive and/or therapeutic approaches for managing NAFLD.
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6.
The Sick Adipose Tissue: New Insights Into Defective Signaling and Crosstalk With the Myocardium.
Bermúdez, V, Durán, P, Rojas, E, Díaz, MP, Rivas, J, Nava, M, Chacín, M, Cabrera de Bravo, M, Carrasquero, R, Ponce, CC, et al
Frontiers in endocrinology. 2021;:735070
Abstract
Adipose tissue (AT) biology is linked to cardiovascular health since obesity is associated with cardiovascular disease (CVD) and positively correlated with excessive visceral fat accumulation. AT signaling to myocardial cells through soluble factors known as adipokines, cardiokines, branched-chain amino acids and small molecules like microRNAs, undoubtedly influence myocardial cells and AT function via the endocrine-paracrine mechanisms of action. Unfortunately, abnormal total and visceral adiposity can alter this harmonious signaling network, resulting in tissue hypoxia and monocyte/macrophage adipose infiltration occurring alongside expanded intra-abdominal and epicardial fat depots seen in the human obese phenotype. These processes promote an abnormal adipocyte proteomic reprogramming, whereby these cells become a source of abnormal signals, affecting vascular and myocardial tissues, leading to meta-inflammation, atrial fibrillation, coronary artery disease, heart hypertrophy, heart failure and myocardial infarction. This review first discusses the pathophysiology and consequences of adipose tissue expansion, particularly their association with meta-inflammation and microbiota dysbiosis. We also explore the precise mechanisms involved in metabolic reprogramming in AT that represent plausible causative factors for CVD. Finally, we clarify how lifestyle changes could promote improvement in myocardiocyte function in the context of changes in AT proteomics and a better gut microbiome profile to develop effective, non-pharmacologic approaches to CVD.
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7.
Human Milk Drives the Intimate Interplay Between Gut Immunity and Adipose Tissue for Healthy Growth.
van den Elsen, LWJ, Verhasselt, V
Frontiers in immunology. 2021;:645415
Abstract
As the physiological food for the developing child, human milk is expected to be the diet that is best adapted for infant growth needs. There is also accumulating evidence that breastfeeding influences long-term metabolic outcomes. This review covers the potential mechanisms by which human milk could regulate healthy growth. We focus on how human milk may act on adipose tissue development and its metabolic homeostasis. We also explore how specific human milk components may influence the interplay between the gut microbiota, gut mucosa immunity and adipose tissue. A deeper understanding of these interactions may lead to new preventative and therapeutic strategies for both undernutrition and other metabolic diseases and deserves further exploration.
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8.
PPARs-Orchestrated Metabolic Homeostasis in the Adipose Tissue.
Sun, C, Mao, S, Chen, S, Zhang, W, Liu, C
International journal of molecular sciences. 2021;(16)
Abstract
It has been more than three decades since peroxisome proliferator-activated receptors (PPARs) were first discovered. Many investigations have revealed the central regulators of PPARs in lipid and glucose homeostasis in response to different nutrient conditions. PPARs have attracted much attention due to their ability to improve metabolic syndromes, and they have also been proposed as classical drug targets for the treatment of hyperlipidemia and type 2 diabetes (T2D) mellitus. In parallel, adipose tissue is known to play a unique role in the pathogenesis of insulin resistance and metabolic syndromes due to its ability to "safely" store lipids and secrete cytokines that regulate whole-body metabolism. Adipose tissue relies on a complex and subtle network of transcription factors to maintain its normal physiological function, by coordinating various molecular events, among which PPARs play distinctive and indispensable roles in adipocyte differentiation, lipid metabolism, adipokine secretion, and insulin sensitivity. In this review, we discuss the characteristics of PPARs with special emphasis on the roles of the different isotypes in adipocyte biology.
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9.
Significance of Adipose Tissue Maintenance in Patients Undergoing Hemodialysis.
Okuno, S
Nutrients. 2021;(6)
Abstract
In the general population, obesity is known to be associated with adverse outcomes, including mortality. In contrast, high body mass index (BMI) may provide a survival advantage for hemodialysis patients, which is known as the obesity paradox. Although BMI is the most commonly used measure for the assessment of obesity, it does not distinguish between fat and lean mass. Fat mass is considered to serve as an energy reserve against a catabolic condition, while the capacity to survive starvation is also thought to be dependent on its amount. Thus, fat mass is used as a nutritional marker. For example, improvement of nutritional status by nutritional intervention or initiation of hemodialysis is associated with an increase in fat mass. Several studies have shown that higher levels of fat mass were associated with better survival in hemodialysis patients. Based on body distribution, fat mass is classified into subcutaneous and visceral fat. Visceral fat is metabolically more active and associated with metabolic abnormalities and inflammation, and it is thus considered to be a risk factor for cardiovascular disease and mortality. On the other hand, subcutaneous fat has not been consistently linked to adverse phenomena and may reflect nutritional status as a type of energy storage. Visceral and subcutaneous adipose tissues have different metabolic and inflammatory characteristics and may have opposing influences on various outcomes, including mortality. Results showing an association between increased subcutaneous fat and better survival, along with other conditions, such as cancer or cirrhosis, in hemodialysis patients have been reported. This evidence suggests that fat mass distribution (i.e., visceral fat and subcutaneous fat) plays a more important role for these beneficial effects in hemodialysis patients.
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10.
The Role of Exercise, Diet, and Cytokines in Preventing Obesity and Improving Adipose Tissue.
Atakan, MM, Koşar, ŞN, Güzel, Y, Tin, HT, Yan, X
Nutrients. 2021;(5)
Abstract
The prevalence of obesity continues to rise worldwide despite evidence-based public health recommendations. The promise to adopt a healthy lifestyle is increasingly important for tackling this global epidemic. Calorie restriction or regular exercise or a combination of the two is accepted as an effective strategy in preventing or treating obesity. Furthermore, the benefits conferred by regular exercise to overcome obesity are attributed not only to reduced adiposity or reduced levels of circulating lipids but also to the proteins, peptides, enzymes, and metabolites that are released from contracting skeletal muscle or other organs. The secretion of these molecules called cytokines in response to exercise induces browning of white adipose tissue by increasing the expression of brown adipocyte-specific genes within the white adipose tissue, suggesting that exercise-induced cytokines may play a significant role in preventing obesity. In this review, we present research-based evidence supporting the effects of exercise and various diet interventions on preventing obesity and adipose tissue health. We also discuss the interplay between adipose tissue and the cytokines secreted from skeletal muscle and other organs that are known to affect adipose tissue and metabolism.