Activation of Sirtuin 3, a Promising “Head Goose Molecule,” Triggers the Negentropic Mechanism for Treating Metabolic Diseases

Hu Li , Tong Wang , Biao Dong , Zonggen Peng , Jiandong Jiang

Engineering ›› : 202512008

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Engineering ›› :202512008 DOI: 10.1016/j.eng.2025.12.008
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Activation of Sirtuin 3, a Promising “Head Goose Molecule,” Triggers the Negentropic Mechanism for Treating Metabolic Diseases
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Abstract

Metabolic diseases, such as diabetes, obesity, and steatotic liver disease, represent a global epidemic. The pathogenesis of these disorders involves systemic disturbances in glucose homeostasis, lipid metabolism, energy balance, and inflammation, yet effective therapeutic strategies to correct these core disturbances remain limited. Silent information regulator 3 (sirtuin 3 (SIRT3)), a major mitochondrial deacetylase that we defined as the “head goose molecule,” acts as a central regulator and can initiate a coordinated rescue of metabolic homeostasis. We integrate evidence that SIRT3 activation triggers a “negentropic mechanism,” a suite of processes that collectively counteract systemic metabolic disorders by enhancing insulin sensitivity, promoting lipid oxidation, fine-tuning redox equilibrium, optimizing energy expenditure, and suppressing inflammation. The therapeutic potential of SIRT3 activators derived from natural products, synthetic compounds, and nicotinamide adenine dinucleotide (NAD+) precursors is evaluated, highlighting their promise as safe and sustainable treatment options. This review establishes the role of SIRT3 as a master regulator and suggests that it should be targeted to reconstitute systemic metabolic homeostasis.

Keywords

Sirtuin 3 / Metabolic diseases / Head goose molecule / Negentropic mechanism / Sirtuin 3 activator

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Hu Li, Tong Wang, Biao Dong, Zonggen Peng, Jiandong Jiang. Activation of Sirtuin 3, a Promising “Head Goose Molecule,” Triggers the Negentropic Mechanism for Treating Metabolic Diseases. Engineering 202512008 DOI:10.1016/j.eng.2025.12.008

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