bims-adipim 2023-09-24 papers

Issue of 2023–09–24
four papers selected by
Matthew C. Sinton, University of Glasgow

Cell Rep Med. 2023 09 19. pii: S2666-3791(23)00316-6. [Epub ahead of print]4(9): 101163

Boosting NAD: An opportunity for metabolic reprogramming of Th17 cells in psoriatic disease.

Metabolic reprogramming of CD4 T cells has become an opportunity for adjunctive therapies. Here, Han et al. show that boosting NAD+ blunts systemic Th17 responses and increases antioxidant pathways through arginine and fumarate-mediated activation of NRF2 transcription factor.

DOI: https://doi.org/10.1016/j.xcrm.2023.101163

Endocrinology. 2023 Sep 20. pii: bqad143. [Epub ahead of print]

Adipocyte glucocorticoid receptor inhibits immune regulatory genes to maintain immune cell homeostasis in adipose tissue.

Shripa Amatya, Dylan Tietje-Mckinney, Schaefer Mueller, Maria G Petrillo, Matthew D Woolard, Sushma Bharrhan, A Wayne Orr, Christopher G Kevil, John A Cidlowski, Diana Cruz-Topete.

Glucocorticoids acting via the glucocorticoid receptors (GR) are key regulators of metabolism and the stress response. However, uncontrolled or excessive GR signaling adversely affects adipose tissue, including endocrine, immune, and metabolic functions. Inflammation of the adipose tissue promotes systemic metabolic dysfunction; however, the molecular mechanisms underlying the role of adipocyte GR in regulating genes associated with adipose tissue inflammation are poorly understood. We performed in vivo studies using adipocyte specific GR knockout mice (Adipo GRKO) in conjunction with in vitro studies to understand the contribution of adipocyte GR in regulating adipose tissue immune homeostasis. Our findings show that adipocyte specific GR signaling regulates adipokines at both mRNA and plasma levels, and immune regulatory (Coch, Pdcd1, Cemip, and Cxcr2) mRNA gene expression, which affects myeloid immune cell presence in white adipose tissue. We found that in adipocytes, GR directly influences Cxcr2. This chemokine receptor promotes immune cell migration, indirectly affecting Pdcd1 and Cemip gene expression in non-adipocyte or stromal cells. Our findings suggest that GR adipocyte signaling suppresses inflammatory signals, maintaining immune homeostasis. We also found that GR signaling in adipose tissue in response to stress is sexually dimorphic. Understanding the molecular relationship between GR signaling and adipose tissue inflammation could help develop potential targets to improve local and systemic inflammation, insulin sensitivity, and metabolic health.

Keywords: Glucocorticoids; adipose tissue; adipose tissue homeostasis; glucocorticoid receptor

DOI: https://doi.org/10.1210/endocr/bqad143

Curr Opin Genet Dev. 2023 Sep 20. pii: S0959-437X(23)00094-1. [Epub ahead of print]83 102114

Adipose tissue lipid metabolism: lipolysis.

Chung Hwan Cho, Sanil Patel, Prashant Rajbhandari.

White adipose tissue stores fatty acid (FA) as triglyceride in the lipid droplet organelle of highly specialized cells known as fat cells or adipocytes. Depending on the nutritional state and energy demand, hormonal and biochemical signals converge on activating an elegant and fundamental process known as lipolysis, which involves triglyceride hydrolysis to FAs. Almost six decades of work have vastly expanded our knowledge of lipolysis from enzymatic processes to complex protein assembly, disassembly, and post-translational modification. Research in recent decades ushered in the discovery of new lipolytic enzymes and coregulators and the characterization of numerous factors and signaling pathways that regulate lipid hydrolysis on transcriptional and post-transcriptional levels. This review will discuss recent developments with particular emphasis on the past two years in enzymatic lipolytic pathways and transcriptional regulation of lipolysis. We will summarize the positive and negative regulators of lipolysis, the adipose tissue microenvironment in lipolysis, and the systemic effects of lipolysis. The dynamic nature of adipocyte lipolysis is emerging as an essential regulator of metabolism and energy balance, and we will discuss recent developments in this area.

DOI: https://doi.org/10.1016/j.gde.2023.102114

Trends Endocrinol Metab. 2023 Sep 14. pii: S1043-2760(23)00167-4. [Epub ahead of print]

Brain-body communication in metabolic control.

Alessandro Furlan, Paul Petrus.

A thorough understanding of the mechanisms controlling energy homeostasis is needed to prevent and treat metabolic morbidities. While the contribution of organs such as the liver, muscle, adipose tissue, and pancreas to the regulation of energy has received wide attention, less is known about the interplay with the nervous system. Here, we highlight the role of the nervous systems in regulating metabolism beyond the classic hypothalamic endocrine signaling models and discuss the contribution of circadian rhythms, higher brain regions, and sociodemographic variables in the energy equation. We infer that interdisciplinary approaches are key to conceptually advancing the current research frontier and devising innovative therapies to prevent and treat metabolic disease.

Keywords: circadian rhythms; interorgan communication; metabolic disease; metabolism; nervous system

DOI: https://doi.org/10.1016/j.tem.2023.08.014