Postbiotic impact on host metabolism and immunity provides therapeutic potential in metabolic disease.

The gut microbiota influences aspects of metabolic disease, including tissue inflammation, adiposity, blood glucose, insulin, and endocrine control of metabolism. Prebiotics or probiotics are often sought to combat metabolic disease. However, prebiotics lack specificity and can have deleterious bacterial community effects. Probiotics require live bacteria to find a colonization niche sufficient to influence host immunity or metabolism. Postbiotics encompass bacterial-derived components and molecules, which are well-positioned to alter host immunometabolism without relying on colonization efficiency or causing widespread effects on the existing microbiota. Here, we summarize the potential for beneficial and detrimental effects of specific postbiotics related to metabolic disease and the underlying mechanisms of action. Bacterial cell wall components such as lipopolysaccharides, muropeptides, lipoteichoic acids and flagellin have context-dependent effects on host metabolism by engaging specific immune responses. Specific types of postbiotics within broad classes of compounds such as lipopolysaccharides, muropeptides can have opposing effects on endocrine control of host metabolism where certain postbiotics are insulin sensitizers and others promote insulin resistance. Bacterial metabolites such as short chain fatty acids, bile acids, lactate, glycerol, succinate, ethanolamine, and ethanol can be substrates for host metabolism. Postbiotics can fuel host metabolic pathways directly or influence endocrine control of metabolism through immunomodulation or mimicking host-derived hormones. The interaction of postbiotics in the host-microbe relationship should be considered during metabolic inflammation and metabolic disease.

被引量：- 发表：1970

The cortisol awakening response: regulation and functional significance.

In healthy individuals, the majority of cortisol secretion occurs within several hours surrounding morning awakening. A highly studied component of this secretory period is the cortisol awakening response (CAR), the rapid increase in cortisol levels across the first 30-45 min after morning awakening. This strong cortisol burst at the start of the active phase has been proposed to be functional in preparing the organism for the challenges of the upcoming day. Here, we review evidence on key regulatory and functional processes of the CAR and develop an integrative model of its functional role. Specifically, we propose that, in healthy individuals, the CAR is closely regulated by an intricate dual-control system, which draws upon key circadian, environmental and neurocognitive processes to best predict the daily need for cortisol-related action. Fine-tuned CAR expression, in turn, is then assumed to induce potent glucocorticoid action via rapid non-genomic and slower genomic pathways (e.g., affecting circadian clock gene expression) to support and modulate daily activity through relevant metabolic, immunological and neurocognitive systems. We propose that this concerted action is adaptive in mediating two main functions: a primary process to mobilize resources to meet activity-related demands and a secondary process to help the organism counterregulate adverse prior-day emotional experiences.

被引量：1 发表：1970

Adiponectin and Adiponectin Receptors in Atherosclerosis.

Adiponectin is an abundantly secreted hormone that communicates information between the adipose tissue, and the immune and cardiovascular systems. In metabolically healthy individuals, adiponectin is usually found at high levels and helps improve insulin responsiveness of peripheral tissues, glucose tolerance, and fatty acid oxidation. Beyond its metabolic functions in insulin-sensitive tissues, adiponectin plays a prominent role in attenuating the development of atherosclerotic plaques, partially through regulating macrophage-mediated responses. In this context, adiponectin binds to its receptors, adiponectin receptor 1 (AdipoR1) and AdipoR2 on the cell surface of macrophages to activate a downstream signaling cascade and induce specific atheroprotective functions. Notably, macrophages modulate the stability of the plaque through their ability to switch between pro-inflammatory responders, and anti-inflammatory pro-resolving mediators. Traditionally, the extremes of the macrophage polarization spectrum span from M1 pro-inflammatory and M2 anti-inflammatory phenotypes. Previous evidence has demonstrated that the adiponectin-AdipoR pathway influences M1-M2 macrophage polarization; adiponectin promotes a shift towards an M2-like state, whereas AdipoR1- and AdipoR2-specific contributions are more nuanced. To explore these concepts in depth, we discuss in this review the impact of adiponectin and AdipoR1/R2 on 1) metabolic and immune responses, and 2) M1-M2 macrophage polarization, including their ability to attenuate atherosclerotic plaque inflammation, and their potential as therapeutic targets for clinical applications.

被引量：- 发表：1970

Common and uncommon mouse models of growth hormone deficiency.

Mouse models of growth hormone deficiency (GHD) have provided important tools for uncovering the various actions of GH. Nearly 100 years of research using these mouse lines has greatly enhanced our knowledge of the GH/IGF-1 axis. Some of the shared phenotypes of the five "common" mouse models of GHD include reduced body size, delayed sexual maturation, decreased fertility, reduced muscle mass, increased adiposity, and enhanced insulin sensitivity. Since these common mouse lines outlive their normal-sized littermates - and have protection from age-associated disease - they have become important fixtures in the aging field. On the other hand, the twelve "uncommon" mouse models of GHD described herein have tremendously divergent health outcomes ranging from beneficial aging phenotypes (similar to those described for the common models) to extremely detrimental features (such as improper development of the CNS, numerous sensory organ defects, and embryonic lethality). Moreover, advancements in next generation sequencing technologies have led to the identification of an expanding array of genes that are recognized as causative agents to numerous rare syndromes with concomitant GHD. Accordingly, this review provides researchers with a comprehensive up-to-date collection of the common and uncommon mouse models of GHD that have been used to study various aspects of physiology and metabolism associated with multiple forms of GHD. For each mouse line presented, the closest comparable human syndromes are discussed providing important parallels to the clinic.

被引量：- 发表：1970

Current Challenges and Future Directions in the Assessment of Glucocorticoid Status.

被引量：- 发表：1970