Obesity causes systemic inflammation, hepatic and renal damage, as well as gut microbiota dysbiosis. Alternative vegetable sources rich in polyphenols are known to prevent or delay the progression of metabolic abnormalities during obesity. Vachellia farnesiana (VF) is a potent source of polyphenols with antioxidant and anti-inflammatory activities with potential anti-obesity effects. We performed an in vivo preventive or an interventional experimental study in mice and in vitro experiments with different cell types. In the preventive study, male C57BL/6 mice were fed with a Control diet, a high-fat diet, or a high-fat diet containing either 0.1% methyl gallate, 10% powdered VFP, or 0.5%, 1%, or 2% of a polyphenolic extract (PE) derived from VFP (Vachellia farnesiana pods) for 14 weeks. In the intervention study, two groups of mice were fed for 14 weeks with a high-fat diet and then one switched to a high-fat diet with 10% powdered VFP for ten additional weeks. In the in vitro studies, we evaluated the effect of a VFPE (Vachellia farnesiana polyphenolic extract) on glucose-stimulated insulin secretion in INS-1E cells or of naringenin or methyl gallate on mitochondrial activity in primary hepatocytes and C2C12 myotubes. VFP or a VFPE increased whole-body energy expenditure and mitochondrial activity in skeletal muscle; prevented insulin resistance, hepatic steatosis, and kidney damage; exerted immunomodulatory effects; and reshaped fecal gut microbiota composition in mice fed a high-fat diet. VFPE decreased insulin secretion in INS-1E cells, and its isolated compounds naringenin and methyl gallate increased mitochondrial activity in primary hepatocytes and C2C12 myotubes. In conclusion VFP or a VFPE prevented systemic inflammation, insulin resistance, and hepatic and renal damage in mice fed a high-fat diet associated with increased energy expenditure, improved mitochondrial function, and reduction in insulin secretion.

Asprosin is a recently discovered adipokine involved in the regulation of hepatic gluconeogenesis and appetite, but its role in hepatic lipid metabolism, a key aspect of metabolic dysfunction-associated steatotic liver disease (MASLD), is unknown. The aim of this study was to investigate whether asprosin could regulate hepatic lipid metabolism in vitro and in an animal model and to determine the potential association between circulating levels of asprosin and the severity of hepatic steatosis in humans. The effects of asprosin on the metabolic phenotype of mice with diet-induced obesity (DIO), as well as on de novo lipogenesis, β-oxidation, and mitochondrial function, were analyzed in both cultured primary hepatocytes and mice by assessing mRNA and protein levels of metabolic pathway components, along with mitochondrial functional. Furthermore, serum asprosin levels were measured in 314 subjects who also underwent transient elastography. The results showed that in vitro, asprosin reduced expression of lipogenic genes and increased those of fatty acid oxidation and mitochondrial activity in hepatocytes. In the DIO model, asprosin-treated mice showed reduced lipid accumulation, improved metabolic parameters and increased abundance of proteins of lipid catabolism. Furthermore, asprosin levels were positively correlated with the controlled attenuation parameter (CAP) and liver stiffness (KPa) in FibroScan measurements. Higher asprosin levels were observed in subjects with severe steatosis (S2 and S3) compared to those without (S0). This adipokine appears to play a protective role in early hepatic steatosis by modulating lipid metabolism and enhancing mitochondrial function.

Breast cancer (BCa) is a heterogeneous disease, initially responsive to hormone therapy but often developing resistance to both hormonal and chemotherapy treatments. Novel therapeutic strategies are needed for drug-resistant BCa. Genistein, a phytoestrogen structurally similar to estrogen, competes with estrogen for receptor binding and exhibits anti-cancer effects. In this study, we investigated the cellular and metabolic impacts of genistein, alone or in combination with chemotherapy, in two human BCa cell lines—one estrogen receptor-positive (ER+) and one estrogen receptor-negative (ER−). We observed a strong synergistic effect on cell viability at low concentrations of genistein and chemotherapy, resulting in reduced clonogenic capacity and impaired cell migration. Genistein alone modulated cellular energy metabolism, notably reducing ATP production in MCF7 (ER+) cells. This metabolic shift was linked to a decreased dependence on fatty acids for energy, coupled with a decrease in the rate-limiting mitochondrial translocase CPT1 required for fatty acid oxidation, alongside with an increase in intracellular fatty acid levels. While the most significant changes occurred in ER+ cells, ER− cells also showed responses to genistein treatment. Collectively, our findings suggest that low dose genistein, in combination with conventional chemotherapy, induces synergistic anti-cancer effects, promoting cellular senescence. This effect may be partly mediated by a reduced reliance on fatty acid metabolism in BCa cells.