Background: Obesity increases reactive oxygen species production and alters adipokines levels, resulting in a low-grade chronic inflammation state, which contributes to tissue metabolic dysfunction. 10-gingerol, a phenol present in ginger, has shown potential anti-obesogenic effects in vitro. However, the antioxidant and anti-inflammatory properties of 10-gingerol have not been approached. The aim of this study was to investigate the effects of 10-gingerol on antioxidant enzymes’ expression and adipokine production in 3T3-L1 adipocytes in response to lipopolysaccharide (LPS)-induced inflammation. Methods: 10-gingerol antioxidant capacity was assessed through Oxygen Radical Absorbance Capacity (ORAC) , Ferric Reducing Antioxidant Power (FRAP), and radical scavenging activity of 2,2-diphenyl-2-picrylhydrazyl (DPPH) assays. 3T3-L1 cells were differentiated and stimulated with 100 ng/mL LPSs. Then, 15 µg/mL 10-gingerol was added for 48 h. The mRNA expression and protein abundance of antioxidant enzymes were evaluated by qPCR and Western blot, respectively. Adipokine levels were determined by ELISA. Results: 10-gingerol showed low FRAP and DPPH values but a moderate ORAC value. Moreover, 10-gingerol increased Gpx1 and Sod1 but downregulated Cat expression. Additionally, 10-gingerol significantly increased CAT and GPx1 levels but not SOD-1. Finally, adiponectin and leptin concentrations were increased while resistin and tumor necrosis factor alpha (TNFα) were decreased by 10-gingerol. Conclusions: 10-gingerol presented antioxidant potential by increasing antioxidant enzymes and attenuated LPS-induced inflammation by modulating adipokines in 3T3-L1 adipocytes.

Obesity is a global public health concern characterized by low-grade chronic inflammation and metabolic dysregulation. Ginger (Zingiber officinale Roscoe) contains bioactive compounds that have demonstrated potential anti-obesity and immunomodulatory effects. This review aims to synthesize the current evidence regarding the immunometabolic effects of ginger supplementation in obesity, integrating findings from in vitro, in vivo, and clinical studies. Evidence indicates that ginger and its principal compounds, such as 6-gingerol and 6-shogaol, inhibit adipocyte differentiation and lipid accumulation, reduce pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and the chemoattractant protein of monocytes-1 (MCP-1), improve lipid profiles, and enhance anti-inflammatory adipokines like adiponectin. Clinical trials report improvements in insulin sensitivity, reductions in inflammatory markers, and body weight management in individuals with obesity. This review paper also highlights the cellular and molecular mechanisms of immunometabolic effects of ginger and its bioactive compounds. Therefore, ginger supplementation exhibits promising immunometabolic effects with the potential to support the prevention and treatment of obesity and its comorbidities. However, further rigorous clinical trials are necessary to confirm its efficacy and safety as well as its role in complementing existing strategies for obesity management.

Mitochondrial abundance and activity in adipocytes are critical for adequate adipose tissue function and whole-body energy homeostasis. Mitochondrial dysfunction in adipocytes impairs lipid metabolism, insulin sensitivity, and thermogenesis, leading to metabolic diseases. Enhancing mitochondrial function and density in adipose tissue may provide a promising therapeutic approach for metabolic diseases. This study evaluates the effects of a ginger phenol mixture on mitochondrial density and function, AMPK activation, lipid droplet content, and lipolysis markers in adipocytes differentiated in vitro. Pre-adipocytes isolated from the inguinal adipose tissue of Wistar rats were differentiated and assigned to three experimental groups: vehicle (0.2% DMSO), gingerol mixture (6 μg/mL), and positive control (1 mmol/m³ AMPK activator 5-Aminoimidazole-4-carboxamide ribonucleoside). Mitochondrial density and lipid content were assessed by MitoTracker and Bodipy staining respectively, while mitochondrial respiration was evaluated in an Extracellular Flux Analyzer. Protein abundance and basal lipolysis were evaluated by Western blotting and free fatty acids determination in supernatant, respectively. The gingerol mixture significantly enhanced mitochondrial density and respiration, including both maximal and ATP-linked capacities. Additionally, it activated AMPK, upregulated the expression of mitochondrial complexes, enhanced lipolysis markers, and reduced lipid droplet content. These findings suggest that the gingerol mixture enhances mitochondrial function, stimulates lipolysis, and reduces lipid accumulation in adipocytes, contributing to metabolic homeostasis in adipose tissue. This highlights its potential use as a complementary therapeutic agent for the management of obesity.