The global prevalence of obesity and type 2 diabetes has increased considerably in recent decades, primarily due to behavioral changes associated with societal progress, such as increased consumption of high-calorie foods and sedentary lifestyles. Obesity is a disease of the energy homeostasis system, not merely a passive accumulation of fat. The hypothalamus serves as the regulatory center for energy balance, and together with peripheral organs, such as liver, pancreas, muscle and adipose tissue, controls food intake, energy expenditure, and whole-body metabolism. Adenosine, a product of ATP catabolism, exerts its effects through various G-protein-coupled receptors: A1R, A2AR, A2BR, and A3R. It plays a key role in regulating peripheral metabolism, including glucose homeostasis, insulin sensitivity, fat beta-oxidation, and lipolysis in adipose tissue. Beyond its roles in the CNS, adenosine receptors are also crucial in metabolic tissues, where they regulate glucose and lipid homeostasis and contribute to overall metabolic function. Several studies have been analyzing the role of adenosine system, specifically the adenosine receptors in the regulation of whole-body metabolism, and the importance of adenosine receptors in context of metabolic diseases and obesity. In this review, we provide an overview of the adenosine signaling system, highlighting its role in metabolic regulation as well as the pathophysiological mechanisms underlying obesity and type 2 diabetes.

Obesity is a worldwide epidemic disease marked by changes in the function of various tissue and organs, driven by excessive fat accumulation. In recent years obesity was characterized not just by the increase of fat, but also an imbalance of energy homeostasis mechanisms. In parallel with global rise in obesity, the incidence of obesity during pregnancy and lactation had also been steadily increasing. Maternal obesity is a public health issue that affects the child and the mother, in acute and chronic term, being a risk factor for the development of metabolic, hormonal, neurodevelopmental, and psychiatric disorders in offspring. Obesity during the gestation can reprogram the fetal immune, metabolic, endocrine, and neurological systems, influencing offspring's metabolism and mental health. This is supported by the Developmental Origins of Health and Disease (DOHaD) theory, which proposes that environmental factors during critical periods of early development (as the fetal period) can influence the risk of developing diseases later in life. In this review, we focused on how maternal obesity can affect the brain offspring neurodevelopment, neural circuits, synapses, glial cells, and neuroinflammation, which all can influence offspring behavioral disorders. image

Background/Objectives: Caffeine consumption has been reported to have beneficial effects in metabolic disorders; however, its effects on food intake are not fully elucidated. This study evaluated the impact of chronic caffeine consumption on weight gain, food intake, and metabolic parameters in C57BL/6 male mice. Methods: Eight-week-old male mice (28 animals) were divided into four groups: control (chow diet), caffeine (chow diet + 1 g/L caffeine in drinking water), high-fat diet (HFD), and HFD + caffeine (HFD + 1 g/L caffeine in drinking water). Diets and caffeine were provided ad libitum for 8 weeks. Food and water intake were recorded weekly, and blood glucose was measured every 4 weeks. After 8 weeks of diet and caffeine exposure, metabolic tests were conducted, and tissues were collected for biochemical analysis. Results: HFD consumption for 8 weeks induced an increase in body weight and adiposity compared to the chow diet, without changes in food intake. Caffeine consumption prevented body weight gain and adiposity, although it increased food intake. Caffeine also improved glucose tolerance in the HFD mouse model, without changes in random blood glucose, triglyceride, or cholesterol levels. Analysis of hypothalamic neuropeptide (Agrp, NPY, Pomc, Cart), involved in the control of food intake, showed no differences in expression. There were also no changes observed in locomotion nor in anxiety-like behavior. Conclusions: In conclusion, chronic high-fat diet (HFD) exposure induced obesity characterized by increased body weight and adiposity without altering food intake. Chronic caffeine consumption counteracted HFD-induced weight gain and fat accumulation and improved glucose tolerance, despite increasing food intake. Importantly, caffeine consumption in the HFD group did not affect locomotor activity or anxiety-like behavior, suggesting that its metabolic effects are not driven by changes in general activity or emotional state. Overall, these findings indicate that chronic caffeine consumption improves metabolic homeostasis in HFD-fed mice.