The transcription factor hepatocyte nuclear factor 4A acts in the intestine to promote white adipose tissue energy storage

The transcription factor hepatocyte nuclear factor 4 A (HNF4A) controls the metabolic features of several endodermal epithelia. Both HNF4A and HNF4G are redundant in the intestine and it remains unclear whether HNF4A alone controls intestinal lipid metabolism. Here we show that intestinal HNF4A is not required for intestinal lipid metabolism per se, but unexpectedly influences whole-body energy expenditure in diet-induced obesity (DIO). Deletion of intestinal HNF4A caused mice to become DIO-resistant with a preference for fat as an energy substrate and energetic changes in association with white adipose tissue (WAT) beiging. Intestinal HNF4A is crucial for the fat-induced release of glucose-dependent insulinotropic polypeptide (GIP), while the reintroduction of a stabilized GIP analog rescues the DIO resistance phenotype of the mutant mice. Our study provides evidence that intestinal HNF4A plays a non-redundant role in whole-body lipid homeostasis and points to a non-cell-autonomous regulatory circuit for body-fat management.

Biological Markers of Training Level among Qualified Greco-Roman Wrestlers

BACKGROUND: The article presents the dynamics of biochemical indicators showing the tension of body functional systems in qualified Greco-Roman wrestlers at the pre-competition stage. Biochemical indicators can be regarded as the markers of training level, as a reflection of adaptive changes during performing training loads. AIM: The study aims to examine the adaptive reactions of body internal systems in wrestlers to the load performed at the stage of pre-competition training. METHODS: The methodological basis of the study is the examination of the reaction of body functional systems in wrestlers (n = 24) in response to the load performed at the stage of pre-competition training. The basis of the studied indicators of wrestlers’ organisms is the dynamics of the enzymatic activity (ALT and AST), the activity of creatine phosphokinase, and the balance of anabolic and catabolic processes in the course of a 2-week macrocycle of the pre-competition training. RESULTS: A high level of enzymatic activity (ALT and AST) was noted as the response to shock training load in the first and the second training macrocycles against the background of a negative trend during the entire sports event, which indicates a directed decrease in the heart’s tension muscle, being an indicator of adaptive changes occurring in wrestlers’ body energy. The high variability of AST indicators on the first day and creatine phosphokinase throughout the entire pre-competition training pointed out an individual level of adaptive reactions of the athletes’ bodies in response to the training load taken. CONCLUSIONS: The results of the study have shown notable dynamics in the indicators of the enzymatic activity of AST, creatine phosphokinase, and the hormone cortisol in a series of shock training loads, as the response to adaptive changes in body energy systems, the value of which should be considered during the pre-competition training.

The Role of Leptin in the Development of Energy Homeostatic Systems and the Maintenance of Body Weight

LEP is a pleiotropic gene and the actions of leptin extend well beyond simply acting as the signal of the size of adipose tissue stores originally proposed. This is a discussion of the multi-system interactions of leptin with the development of the neural systems regulating energy stores, and the subsequent maintenance of energy stores throughout the lifespan. The prenatal, perinatal, and later postnatal effects of leptin on systems regulating body energy stores and on the energy stores themselves are heavily influenced by the nutritional environment which leptin exposure occurs. This review discusses the prenatal and perinatal roles of leptin in establishing the neuronal circuitry and other systems relevant to the adiposity set-point (or “threshold”) and the role of leptin in maintaining weight homeostasis in adulthood. Therapeutic manipulation of the intrauterine environment, use of leptin sensitizing agents, and identification of specific cohorts who may be more responsive to leptin or other means of activating the leptin signaling pathway are ripe areas for future research.

Extrahypothalamic Control of Energy Balance and Its Connection with Reproduction: Roles of the Amygdala

Body energy and metabolic homeostasis are exquisitely controlled by multiple, often overlapping regulatory mechanisms, which permit the tight adjustment between fuel reserves, internal needs, and environmental (e.g., nutritional) conditions. As such, this function is sensitive to and closely connected with other relevant bodily systems, including reproduction and gonadal function. The aim of this mini-review article is to summarize the most salient experimental data supporting a role of the amygdala as a key brain region for emotional learning and behavior, including reward processing, in the physiological control of feeding and energy balance. In particular, a major focus will be placed on the putative interplay between reproductive signals and amygdala pathways, as it pertains to the control of metabolism, as complementary, extrahypothalamic circuit for the integral control of energy balance and gonadal function.

Stomach secretes estrogen in response to the blood triglyceride levels

Mammals receive body energy information to maintain energy homeostasis. Ghrelin, insulin, leptin and vagal afferents transmit the status of fasting, blood glucose, body fat, and food intake, respectively. Estrogen also inhibits feeding behavior and lipogenesis, but increases body fat mass. However, how blood triglyceride levels are monitored and the physiological roles of estrogen from the perspective of lipid homeostasis remain unsettled. Here, we show that stomach secretes estrogen in response to the blood triglyceride levels. Estrogen-secreting gastric parietal cells predominantly use fatty acids as an energy source. Blood estrogen levels increase as blood triglyceride levels rise in a stomach-dependent manner. Estrogen levels in stomach tissues increase as blood triglyceride levels rise, and isolated gastric gland epithelium produces estrogen in a fatty acid-dependent manner. We therefore propose that stomach monitors and controls blood triglyceride levels using estrogen, which inhibits feeding behavior and lipogenesis, and promotes triglyceride uptake by adipocytes.

Paracrine role for endothelial IGF-1 receptor in white adipocyte beiging

SummaryThere are at least two distinct types of thermogenic adipocyte in mammals: a pre-existing form established during development, termed classical brown adipocytes and an inducible form, ‘beige’ adipocytes1–3. Various environmental cues can stimulate a process frequently referred to as ‘beiging’ of white adipose tissue (WAT), leading to enhanced thermogenesis and obesity resistance 4, 5. Whilst beiging of WAT as a therapeutic goal for obesity and obesity-related complications has attracted much attention6–9; therapeutics stimulating beiging without deleterious side-effects remain elusive10. The endothelium lines all blood vessels and is therefore in close proximity to all cells. Many studies support the possibility that the endothelium acts as a paracrine organ11–14. We explored the potential role of endothelial insulin-like growth factor-1 receptor (IGF-1R) as a paracrine modulator of WAT phenotype. Here we show that a reduction in endothelial IGF-1R expression in the presence of nutrient excess leads to white adipocyte beiging, increases whole-body energy expenditure and enhances insulin sensitivity via a non-cell autonomous paracrine mechanism. We demonstrate that this is mediated by endothelial release of malonic acid, which we show, using prodrug analogues, has potentially therapeutically-relevant properties in the treatment of metabolic disease.

microRNAs in Human Adipose Tissue Physiology and Dysfunction

In recent years, there has been a large amount of evidence on the role of microRNA (miRNA) in regulating adipose tissue physiology. Indeed, miRNAs control critical steps in adipocyte differentiation, proliferation and browning, as well as lipolysis, lipogenesis and adipokine secretion. Overnutrition leads to a significant change in the adipocyte miRNOME, resulting in adipose tissue dysfunction. Moreover, via secreted mediators, dysfunctional adipocytes may impair the function of other organs and tissues. However, given their potential to control cell and whole-body energy expenditure, miRNAs also represent critical therapeutic targets for treating obesity and related metabolic complications. This review attempts to integrate present concepts on the role miRNAs play in adipose tissue physiology and obesity-related dysfunction and data from pre-clinical and clinical studies on the diagnostic or therapeutic potential of miRNA in obesity and its related complications.

“Like a Vibration Cascading through the Body”: Energy-Like Somatic Experiences Reported by Western Buddhist Meditators

There are numerous historical and textual references to energy-like somatic experiences (ELSEs) from religious traditions, and even a few psychological studies that have documented related phenomena. However, ELSEs remain an understudied effect of meditation in contemporary research. Based upon narratives from a large qualitative sample of Buddhist meditators in the West reporting meditation-related challenges, this paper offers a unique glimpse into how ELSEs play out in the lives of contemporary meditation practitioners and meditation experts. Departing from studies presuming a “kundalini awakening” framework, this paper presents a broader scope for understanding ELSEs by describing the metaphors practitioners used when speaking about them; the trajectories and impacts of ELSEs, including the factors that were reported as influencing their nature or trajectory; the various ways in which they were interpreted and appraised by practitioners, teachers, and specialists, such as doctors and therapists; and how practitioners responded to them or managed them with particular remedies. Deciding how to interpret and manage ELSEs entailed recruiting frameworks from within and/or beyond the meditator’s specific Buddhist lineage.

The New Role of AMP-Activated Protein Kinase in Regulating Fat Metabolism and Energy Expenditure in Adipose Tissue

Obesity is characterized by excessive accumulation of fat in the body, which is triggered by a body energy intake larger than body energy consumption. Due to complications such as cardiovascular diseases, type 2 diabetes (T2DM), obstructive pneumonia and arthritis, as well as high mortality, morbidity and economic cost, obesity has become a major health problem. The global prevalence of obesity, and its comorbidities is escalating at alarming rates, demanding the development of additional classes of therapeutics to reduce the burden of disease further. As a central energy sensor, the AMP-activated protein kinase (AMPK) has recently been elucidated to play a paramount role in fat synthesis and catabolism, especially in regulating the energy expenditure of brown/beige adipose tissue and the browning of white adipose tissue (WAT). This review discussed the role of AMPK in fat metabolism in adipose tissue, emphasizing its role in the energy expenditure of brown/beige adipose tissue and browning of WAT. A deeper understanding of the role of AMPK in regulating fat metabolism and energy expenditure can provide new insights into obesity research and treatment.