Obesity is characterized by profound alterations in adipose tissue (AT) biology, leading to whole body metabolic disturbances such as insulin resistance and cardiovascular diseases. These alterations are related to the development of a local inflammation, fibrosis, hypertrophy of adipocytes, and dysregulation in energy homeostasis, notably in visceral adipose tissue (VAT). Omega 3 (n-3) fatty acids (FA) have been described to possess beneficial effects against obesity-related disorders, including in the AT; however, the long-term effect across generations remains unknown. The current study was conducted to identify if supplementation with n-3 polyunsaturated FA (PUFA) for three generations could protect from the consequences of an obesogenic diet in VAT. Young mice from the third generation of a lineage receiving a daily supplementation (1% of the diet) with fish oil rich in eicosapentaenoic acid (EPA) or an isocaloric amount of sunflower oil, were fed a high-fat, high-sugar content diet for 4 months. We explore the transcriptomic adaptations in each lineage using DNA microarray in VAT and bioinformatic exploration of biological regulations using online databases. Transgenerational intake of EPA led to a reduced activation of inflammatory processes, perturbation in metabolic homeostasis, cholesterol metabolism, and mitochondrial functions in response to the obesogenic diet as compared to control mice from a control lineage. This suggests that the continuous intake of long chain n-3 PUFA could be preventive in situations of oversupply of energy-dense, nutrient-poor foods.