Helena Cristina Lima Barbosa

The “Gastrointestinal Circuit” is a practical and accessible active learning strategy that improves undergraduate understanding of gastrointestinal physiology. Using visually engaging vinyl banners, it helps clarify complex concepts. Students showed significant knowledge gains from pre- to posttest, and those who participated in the circuit outperformed a previous cohort who did not engage in the activity. These results support the circuit as an effective tool for enhancing learning in physiology education.

Ageing leads to changes in body composition, including increased adiposity and reduced skeletal muscle mass and force. The alterations in ageing skeletal muscle result from impaired proteostasis driven by factors such as chronic inflammation, hormonal changes and reduced nutrient absorption. Those age‐related changes in body composition and skeletal muscle compromise mobility and increase the risk of falls, fractures and metabolic disorders. Tauroursodeoxycholic acid (TUDCA), a bile acid with known benefits in chronic diseases, has been shown by our group to improve cognition and metabolic homeostasis in ageing and Alzheimer's disease mouse models. Interestingly, in previous studies, TUDCA treatment was also associated with increased skeletal muscle mass in ageing mice, leading us to hypothesize that TUDCA could target skeletal muscle to reduce age‐related muscle loss. To explore this, we treated 18‐month‐old C57BL/6 mice with TUDCA or vehicle for 20 days, using 3‐month‐old mice as a young control group. We demonstrate that TUDCA treatment decreases body weight while increasing skeletal muscle mass, restores muscle fibre size and preserves functional integrity. Additionally, TUDCA enhances skeletal muscle insulin sensitivity through increased AKT activation and reduces tissue inflammation. Such improvements collectively support the restoration of skeletal muscle proteostasis, as indicated by increased protein synthesis and phosphorylation of key anabolic signalling pathways, including ribosomal protein S6 kinase beta‐1 (P70S6K) and eukaryotic translation initiation factor 4E‐binding protein 1 (4EBP1). These findings contribute to a better understanding of TUDCA's actions on skeletal muscles of ageing mice and highlight its role as a promising strategy against age‐related muscle loss. image Key points: Tauroursodeoxycholic acid (TUDCA) treatment attenuates skeletal muscle loss in ageing mice. TUDCA improves skeletal muscle insulin sensitivity and restores AKT signalling. TUDCA exerts an anti‐inflammatory effect in skeletal muscle of ageing mice. TUDCA emerges as a potential therapy for age‐related skeletal muscle loss.

Hypothalamic inflammation represents a central mechanism linking obesity to metabolic dysfunction. This process involves glial activation and persistent innate immune signaling, with Toll-like receptor 4 (TLR4) emerging as a critical interface between inflammatory pathways and impaired central insulin signaling. Irisin, a myokine released in response to physical exercise, has been shown to exert metabolic and anti-inflammatory effects in peripheral tissues, as well as neuroprotective actions in the brain. However, whether irisin directly modulates obesity-associated hypothalamic inflammation, particularly through TLR4-dependent pathways, remains unknown. Here, we investigated the effects of short-term intracerebroventricular delivery of recombinant irisin on hypothalamic inflammatory signaling in diet-induced obese mice. Central irisin administration reduced glial reactivity, downregulated components of the TLR4/MyD88 pathway, and increased the expression of anti-inflammatory cytokines in the hypothalamus. In addition, irisin restored insulin-stimulated AKT phosphorylation and selectively reduced inguinal white adipose tissue mass without affecting overall body weight. Together, these findings indicate that central irisin administration attenuates obesity-related hypothalamic inflammation and modulates central insulin signaling, supporting a role for irisin as a regulator of neuroinflammation-linked metabolic dysfunction. Graphical Abstract Graphical abstract created with Biorender.com under publication license (MR296VUFQG).

Over the past decades, bile acids have been recognized as important signaling molecules with significant roles in metabolic health and disease. Many of their beneficial effects are mediated through the activation of the Takeda G protein-coupled receptor 5 (TGR5), a G protein-coupled receptor ubiquitously expressed in both humans and animals. Upon activation, TGR5 stimulates adenylate cyclase, leading to increased cyclic adenosine monophosphate (cAMP) levels and subsequent activation of protein kinase A (PKA). PKA then phosphorylates and activates several downstream signaling pathways, including exchange protein directly activated by cAMP (EPAC), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein kinase B (AKT). Through these pathways, TGR5 acts as a key molecular link between bile acid signaling and the regulation of energy metabolism. TGR5 activation has been associated with body weight loss in obese models, primarily by reducing food intake, enhancing thermogenesis in adipose tissue and muscle to increase energy expenditure, and improving insulin secretion. This review highlights recent advances in our understanding of TGR5 biology and critically examines its therapeutic potential, limitations, and controversies in the context of energy metabolism, offering new perspectives and opportunities for treating metabolic disorders.

Although most studies associate central fibroblast growth factor 19 (FGF19) with reduced food intake, our findings highlight its role in enhancing thermogenesis in white and brown adipose tissues through sympathetic activation. Central FGF19 not only regulates feeding but also drives peripheral adaptations critical for energy homeostasis and body weight control under obesogenic conditions. These insights underscore the significance of top-down mechanisms in FGF19 action and its therapeutic potential for combating obesity.

Obesity is a serious health problem worldwide and the search for new control methods and therapies is imperative. Studies indicate that a variety of obesogenic diets may increase the risk of developing type 2 diabetes mellitus (T2D) by causing insulin resistance in peripheral tissues. The chronic increase in free fatty acids associated with obesity may increase insulin demand by pancreatic beta cells and induce intrinsic beta cell dysfunction through endoplasmic reticulum (ER) stress, which is associated with beta cell loss during the development of T2D. Physical exercise approaches have been emerging as powerful tools and adjuncts in a variety of conditions, improving glucose homeostasis, oxygen uptake, and metabolism. Here, we showed that a 16-week endurance training program mitigated the deleterious effects of an obesogenic diet on glycemic homeostasis, insulin secretion, and ER stress markers as well as islet health markers in C57/BL6 obese mice. The results corroborated the assumption that physical exercise is an effective therapy to avoid beta cell death in glucose metabolism dysfunction and T2D in obese individuals.

We developed “Who Am I?—Cellular Signal Transduction Edition” to assist students in comprehending concepts of cellular signal transduction. This simple and cost-effective tool is perfect for educational settings with limited resources, and it encourages active learning for both small and large groups. Pre- and posttests have shown that it effectively enhances knowledge of hormonal actions and cellular signaling. Positive feedback from students emphasizes its value in reinforcing understanding and improving classroom engagement, making it a promising educational tool.

Impaired insulin production and/or secretion by pancreatic beta cells can lead to high blood glucose levels and type 2 diabetes (T2D). Therefore, investigating new proteins involved in beta cell response to stress conditions could be useful in finding new targets for therapeutic approaches. KH-type splicing regulatory protein (KSRP) is a protein usually involved in gene expression due to its role in post-transcriptional regulation. Although there are studies describing the important role of KSRP in tissues closely related to glucose homeostasis, its effect on pancreatic beta cells has not been explored so far. Pancreatic islets from diet-induced obese mice (C57BL/6JUnib) were used to determine KSRP expression and we also performed in vitro experiments exposing INS-1E cells (pancreatic beta cell line) to different stressors (palmitate or cyclopiazonic acid—CPA) to induce cellular dysfunction. Here we show that KSRP expression is reduced in all the beta cell dysfunction models tested. In addition, when manipulated to knock down KSRP, beta cells exhibited increased death and impaired insulin secretion, whereas KSRP overexpression prevented cell death and increased insulin secretion. Taken together, our findings suggest that KSRP could be an important target to protect beta cells from impaired functioning and death.