Life Metabolism

VOLUME 2 | ISSUE 4 | Aug 2023


Jinke Cheng, Edward T H Yeh · 24 Apr 2023 load017

The Chouchani lab recently reported in Nature that a dynamic intracellular lactate is a physiological regulator for cell cycle progress. They also showed that accumulated lactate in cell mitosis directly binds and inhibits Sentrin/SUMO-specific protease 1 (SENP1) to enrich SUMO2/3-modification of anaphase-promoting complex 4 (APC4), which promotes the degradation of APC/C complexes, leading to mitosis exit.

Hailan Liu, Hongjie Li, Yong Xu · 12 Jun 2023 load024

In a recent study published in Science, Weaver et al. provided insights into the effects of hunger on longevity. Inducing a state of hunger, either through restricting isoleucine intake or by stimulating R50H05 hunger neurons, resulted in an extension of lifespan in fruit flies. This effect is mediated by the modulation of histone proteins in the brain.

Fang Xiao, Zheng Sun · 14 Jun 2023 load025

A recent study shed light on transcriptional regulation of myofiber-derived Dkk3, a secreted protein involved in muscle differentiation, which has therapeutic implications in damage-induced muscle regeneration and obesity-associated muscle atrophy.


Vishal Musale, David H Wasserman, Li Kang · 26 May 2023 load021

Obesity causes extracellular matrix (ECM) remodelling which can develop into serious pathology and fibrosis, having metabolic effects in insulin-sensitive tissues. The ECM components may be increased in response to overnutrition. This review will focus on specific obesity-associated molecular and pathophysiological mechanisms of ECM remodelling and the impact of specific interactions on tissue metabolism. In obesity, complex network of signalling molecules such as cytokines and growth factors have been implicated in fibrosis. Increased ECM deposition contributes to the pathogenesis of insulin resistance at least in part through activation of cell surface integrin receptors and CD44 signalling cascades. These cell surface receptors transmit signals to the cell adhesome which orchestrates an intracellular response that adapts to the extracellular environment. Matrix proteins, glycoproteins, and polysaccharides interact through ligand-specific cell surface receptors that interact with the cytosolic adhesion proteins to elicit specific actions. Cell adhesion proteins may have catalytic activity or serve as scaffolds. The vast number of cell surface receptors and the complexity of the cell adhesome have made study of their roles challenging in health and disease. Further complicating the role of ECM-cell receptor interactions is the variation between cell types. This review will focus on recent insights gained from studies of two highly conserved, ubiquitously axes and how they contribute to insulin resistance and metabolic dysfunction in obesity. These are the collagen-integrin receptor-IPP (ILK-PINCHParvin) axis and the hyaluronan-CD44 interaction. We speculate that targeting ECM components or their receptor-mediated cell signalling may provide novel insights into the treatment of obesity-associated cardiometabolic complications.

Mengxue Sun, Yongwen Wan, Mengjie Shi, Zhuo-Xian Meng, Wenwen Zeng · 06 Jun 2023 load022

Efficient communication between the brain and peripheral organs is indispensable for regulating physiological function and maintaining energy homeostasis. The peripheral nervous system (PNS) in vertebrates, consisting of the autonomic and somatic nervous systems, bridges the peripheral organs and the central nervous system (CNS). Metabolic signals are processed by both vagal sensory nerves and somatosensory nerves. The CNS receives sensory inputs via ascending nerves, serves as the coordination and integration center, and subsequently controls internal organs and glands via descending nerves. The autonomic nervous system consists of sympathetic and parasympathetic branches that project peripheral nerves into various anatomical locations to regulate the energy balance. Sympathetic and parasympathetic nerves typically control the reflexive and involuntary functions in organs. In this review article, we outline the innervation of adipose tissue, gut, pancreas, and liver, to illustrate the neurobiological basis of central–peripheral interactions. We emphasize the importance of understanding the functional atlas of neural control of energy metabolism, and more importantly, provide potential avenues for further research in this area.


Dominik Pretz, Philip M Heyward, Jeremy Krebs, Joel Gruchot, Charles Barter, Pat Silcock, Nerida Downes, Mohammed Zubair Rizwan, Alisa Boucsein, Julia Bender, Elaine J Burgess, Geke Aline Boer, Pramuk Keerthisinghe, Nigel B Perry, Alexander Tups · 18 Jun 2023 load026

Butein, a rare chalcone found in the toxic plant Toxicodendron vernicifluum, has been shown to regulate glucose homeostasis via inhibition of the nuclear factor kappa-B kinase subunit beta (IKKβ)/nuclear factor kappa B (NF-κB) pathway in the brain. Here, we investigated whether the non-poisonous plant Dahlia pinnata could be a source of butein as a potential treatment for type 2 diabetes (T2D). In mice fed a high-fat diet (HFD) to induce glucose intolerance, an oral D. pinnata petal extract improved glucose tolerance at doses of 3.3 mg/kg body weight and 10 mg/kg body weight. Surprisingly, this effect was not mediated by butein alone but by butein combined with the closely related flavonoids, sulfuretin and/or isoliquiritigenin. Mechanistically, the extract improved systemic insulin tolerance. Inhibition of phosphatidylinositol 3-kinase to block insulin signalling in the brain abrogated the glucoregulatory effect of the orally administered extract. The extract reinstated central insulin signalling and normalized astrogliosis in the hypothalamus of HFD-fed mice. Using NF-κB reporter zebrafish to determine IKKβ/NF-κB activity, a potent anti-inflammatory action of the extract was found. A randomized controlled cross-over clinical trial on participants with prediabetes or T2D confirmed the safety and efficacy of the extract in humans. In conclusion, we identified an extract from flower petals of D. pinnata as a novel treatment option for T2D, potentially targeting the central regulation of glucose homeostasis as a root cause of the disease.


· 16 Jun 2023 load023