Adipose tissue usually is classified as either white, brown or beige/brite, based on whether it functions as an energy storage or thermogenic organ (Cannon and Nedergaard, 2004;Rosen and Spiegelman, 2014). It serves as an important regulator of systemic metabolism, exemplified by the fact that dysfunctional adipose tissue in obesity leads to a host of secondary metabolic complications such as diabetes, cardiovascular diseases and cancer (Hajer et al., 2008;Lauby-Secretan et al., 2016). In addition, adipose tissue is an important endocrine organ, which regulates the function of other metabolic tissues through paracrine and endocrine signals (Scheele and Wolfrum, 2019;Scherer, 2006). Work in recent years has demonstrated that tissue heterogeneity is an important factor regulating the functionality of various organs (Cao et al., 2017;Ginhoux et al., 2016;Park et al., 2018). Here we used single nucleus analysis in mice and men to deconvolute adipocyte heterogeneity. We are able to identify a novel subpopulation of adipocytes whose abundance is low in mice (2-8%) and which is increased under higher ambient temperatures. Interestingly, this population is abundant in humans who live close to thermoneutrality. We demonstrate that this novel adipocyte subtype functions as a paracrine cell regulating the activity of brown adipocytes through acetate-mediated regulation of thermogenesis. These findings could explain, why human brown adipose tissue is substantially less active than mouse tissue and targeting this pathway in humans might be utilized to restore thermogenic activity of this tissue..

Background: Decreased levels of the neuroprotective growth factors, low-grade inflammation, and reduced neurocognitive functions during aging are associated with neurodegenerative diseases, such as Alzheimer’s disease. Physical exercise modifies these disadvantageous phenomena while a sedentary lifestyle promotes them. Purpose: The purposes of the present study included investigating whether both aerobic and resistance exercise produce divergent effects on the neuroprotective growth factors, inflammatory cytokines, and neurocognitive performance, and further exploring whether changes in the levels of these molecular biomarkers are associated with alterations in neurocognitive performance. Methods: Fifty-five older adults with amnestic MCI (aMCI) were recruited and randomly assigned to an aerobic exercise (AE) group, a resistance exercise (RE) group, or a control group. The assessment included neurocognitive measures [e.g., behavior and event-related potential (ERP)] during a task-switching paradigm, as well as circulating neuroprotective growth factors (e.g., BDNF, IGF-1, VEGF, and FGF-2) and inflammatory cytokine (e.g., TNF-α, IL-1β, IL-6, IL-8, and IL-15) levels at baseline and after either a 16-week aerobic or resistance exercise intervention program or a control period. Results: Aerobic and resistance exercise could effectively partially facilitate neurocognitive performance [e.g., accuracy rates (ARs), reaction times during the heterogeneous condition, global switching cost, and ERP P3 amplitude] when the participants performed the task switching paradigm although the ERP P2 components and P3 latency could not be changed. In terms of the circulating molecular biomarkers, the 16-week exercise interventions did not change some parameters (e.g., leptin, VEGF, FGF-2, IL-1β, IL-6, and IL-8). However, the peripheral serum BDNF level was significantly increased, and the levels of insulin, TNF-α, and IL-15 levels were significantly decreased in the AE group, whereas the RE group showed significantly increased IGF-1 levels and decreased IL-15 levels. The relationships between the changes in neurocognitive performance (AR and P3 amplitudes) and the changes in the levels of neurotrophins (BDNF and IGF-1)/inflammatory cytokines (TNF-α) only approached significance. Conclusion: These findings suggested that in older adults with aMCI, not only aerobic but also resistance exercise is effective with regard to increasing neurotrophins, reducing some inflammatory cytokines, and facilitating neurocognitive performance. However, the aerobic and resistance exercise modes likely employed divergent molecular mechanisms on neurocognitive facilitation.

Neurological, neurodegenerative, and psychiatric disorders represent a serious burden because of their increasing prevalence, risk of disability, and the lack of effective causal/disease-modifying treatments. There is a growing body of evidence indicating potentially favourable effects of carnosine, which is an over-the-counter food supplement, in peripheral tissues. Although most studies to date have focused on the role of carnosine in metabolic and cardiovascular disorders, the physiological presence of this di-peptide and its analogues in the brain together with their ability to cross the blood-brain barrier as well as evidence from in vitro, animal, and human studies suggest carnosine as a promising therapeutic target in brain disorders. In this review, we aim to provide a comprehensive overview of the role of carnosine in neurological, neurodevelopmental, neurodegenerative, and psychiatric disorders, summarizing current evidence from cell, animal, and human cross-sectional, longitudinal studies, and randomized controlled trials.