Endocrine Abstracts

Obesity (OB) and type-2 diabetes (T2D) are chronic endocrine-metabolic diseases, associated to insulin-resistance (IR), that represent capital health problems. Fortunately, both pathologies are, at least, partially reversible by dietary interventions, but the potential metabolic, molecular, cellular factors and mechanisms that might be involved in the total/partial reversion of OB/IR/T2D by dietary interventions are poorly known. Thus, in this work, we aimed evaluate the impact of Mediterranean-diet (MedD) and a low-fat-diet (LFD) on the reversion of OB/IR/T2D, and the associated metabolic/cellular/molecular alterations in key tissues [e.g. visceral adipose tissue (VAT) and liver]. To that end, 8-weeks old littermate-male-mice were fed a high-fat diet [HFD; 60% fat (54.2% lard + 5.6% soybean oil)] to develop OB/IR, or a control-diet [17.4% fat (soybean oil), (n=12] for 14-weeks. Then, HFD group mice (with OB/IR) were divided into 3 groups with different diet interventions for additional 13-weeks: i) maintained with the same HFD (n=12); ii) shifted to MedD [35% fat: 21.7% MUFA (extra virgin olive-oil), 5.9% PUFA (4.9% corn-oil+1% fish-oil), and 6.9% SFA (butter); (n=18]; or, iii) shifted to a LFD [30.1% fat: 12.7% MUFA (extra virgin olive oil), 6.8% PUFA (5.7% corn-oil+1.1% fish-oils) and 9.7% SFA (butter); (n=18], while the control-diet group continued with the same diet for a total of 27 weeks. Before and after diet intervention, body-status (weight and composition), glucose homeostasis, indirect calorimetry, and activity as well as plasma insulin, leptin, ghrelin, and ALT were measured. Finally, alterations in the expression of inflammasome- and proliferation-related genes were measured in VAT and liver. As main results, we could observe that both MedD and LFD significantly reversed the OB/IR/metabolic-status induced by HFD (i.e. decreased body/tissue weights, body fat mass, VAT adipocytes area, liver triglyceride content, and pr\oliferation-related genes expression in VAT and liver; improved glucose/insulin tolerance; reestablished respiratory exchange ratio, energy expenditure and activity; recovered plasma insulin/leptin/ghrelin/ALT levels), close to the levels found in the control-diet group. Additionally, MedD/lFD reduced inflammasome-related genes expression vs HFD group in VAT. However, this inflammatory profile was only reverted in the liver of MedD, but not LFD, group vs HFD-group. All toghether, we can conclude that MedD and LFD intervention successfully reverted OB/IR/metabolic-status, but the molecular fingerprints associated to this beneficial effects at the VAT and liver are distinct.

Fundings: CIBERobn (OBN20PI02/2020), and MICINN (PID2022-1381850B-I00).