Trends in Endocrinology and Metabolism最新文献

Cellular turnover is fundamental for tissue homeostasis and integrity. Adipocyte turnover, accounting for 4% of the total cellular mass turnover in humans, is essential for adipose tissue homeostasis during metabolic stress. In obesity, an altered adipose tissue microenvironment promotes adipocyte death. To clear dead adipocytes, macrophages are recruited and form a distinctive structure known as crown-like structure; subsequently, new adipocytes are generated from adipose stem and progenitor cells in the adipogenic niche to replace dead adipocytes. Accumulating evidence indicates that adipocyte death, clearance, and adipogenesis are sophisticatedly orchestrated during adipocyte turnover. In this Review, we summarize our current understandings of each step in adipocyte turnover, discussing its key players and regulatory mechanisms.

Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA), have important roles in human nutrition and brain health by promoting neuronal functions, maintaining inflammatory homeostasis, and providing structural integrity. As Alzheimer's disease (AD) pathology progresses, DHA metabolism in the brain becomes dysregulated, the timing and extent of which may be influenced by the apolipoprotein E ε4 (APOE4) allele. Here, we discuss how maintaining adequate DHA intake early in life may slow the progression to AD dementia in cognitively normal individuals with APOE4, how recent advances in DHA brain imaging could offer insights leading to more personalized preventive strategies, and how alternative strategies targeting PUFA metabolism pathways may be more effective in mitigating disease progression in patients with existing AD dementia.

The worldwide prevalence of cardiometabolic diseases (CMD) is increasing, and emerging evidence implicates the gut microbiota in this multifactorial disease development. Bacteriophages (phages) are viruses that selectively target a bacterial host; thus, phage therapy offers a precise means of modulating the gut microbiota, limiting collateral damage on the ecosystem. Several studies demonstrate the potential of phages in human disease, including alcoholic and steatotic liver disease. In this opinion article we discuss the potential of phage therapy as a predefined medicinal product for CMD and discuss its current challenges, including the generation of effective phage combinations, product formulation, and strict manufacturing requirements.

Eating behaviour and circadian rhythms are closely related. The type, timing, and quantity of food consumed, and host circadian rhythms, directly influence the intestinal microbiota, which in turn impacts host circadian rhythms and regulates food intake beyond homeostatic eating. This Opinion discusses the impact of food intake and circadian disruptions induced by an obesogenic environment on gut-brain axis signalling. We also explore potential mechanisms underlying the effects of altered gut microbiota on food intake behaviour and circadian rhythmicity. Understanding the crosstalk between gut microbiota, circadian rhythms, and unhealthy eating behaviour is crucial to addressing the obesity epidemic, which remains one of the biggest societal challenges of our time.

Axon regeneration requires the mobilization of intracellular resources, including proteins, lipids, and nucleotides. After injury, neurons need to adapt their metabolism to meet the biosynthetic demands needed to achieve axonal regeneration. However, the exact contribution of cellular metabolism to this process remains elusive. Insights into the metabolic characteristics of proliferative cells may illuminate similar mechanisms operating in axon regeneration; therefore, unraveling previously unappreciated roles of metabolic adaptation is critical to achieving neuron regrowth, which is connected to the therapeutic strategies for neurological conditions necessitating nerve repairs, such as spinal cord injury and stroke. Here, we outline the metabolic role in axon regeneration and discuss factors enhancing nerve regrowth, highlighting potential novel metabolic treatments for restoring nerve function.

Autophagy is critical for energy homeostasis and the function of organelles such as endoplasmic reticulum (ER) and mitochondria. Dysregulated autophagy due to aging, environmental factors, or genetic predisposition can be an underlying cause of not only diabetes through β-cell dysfunction and metabolic inflammation, but also diabetic complications such as diabetic kidney diseases (DKDs). Dysfunction of lysosomes, effector organelles of autophagic degradation, due to metabolic stress or nutrients/metabolites accumulating in metabolic diseases is also emerging as a cause or aggravating element in diabetes and its complications. Here, we discuss the etiological role of dysregulated autophagy and lysosomal dysfunction in diabetes and a potential role of autophagy or lysosomal modulation as a new avenue for treatment of diabetes and its complications.