Prebiotics ameliorate dysbiosis and influence metabolism and the immune system, but their effects on cardiovascular complications in metabolic disorders remain largely unknown. We here investigated the effects of the soluble fiber inulin on cardiac, adipose tissue, and hepatic pathology as well as on metabolic disorders in DahlS.Z-Leprfa/Leprfa (DS/obese) rats, an animal model of metabolic syndrome (MetS). DS/obese rats and their homozygous lean (DahlS.Z-Lepr+/Lepr+, or DS/lean) littermate controls were fed a purified diet containing 5% or 20% inulin from 9 to 13 weeks of age. The high-fiber diet ameliorated hypertension, left ventricular inflammation, fibrosis, and diastolic dysfunction, attenuated adipose tissue inflammation and fibrosis as well as alleviated the elevation of interleukin-6 levels, without affecting insulin resistance, in DS/obese rats. In addition, high fiber intake ameliorated lipid accumulation, inflammation, and fibrosis, attenuated the reduction in AMPK activity and the up-regulation of sterol regulatory element binding protein-1c gene expression, and further increased the expression of microsomal triglyceride transfer protein gene, in the liver of DS/obese rats. It also mitigated increases in total and non-high-density lipoprotein-cholesterol levels but increased the triglyceride concentration in serum in these rats. None of these parameters was affected by high dietary fiber in DS/lean rats. The proportion of regulatory T cells in adipose tissue was influenced by dietary fiber but not by genotype. Our results indicate that inulin exacerbates hypertriglyceridemia but alleviates hypertension and cardiac injury as well as adipose tissue and hepatic pathology in MetS rats.

Objectives Evidence suggests that visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) should be considered as distinct types of white fat. Although VAT plays a key role in metabolic syndrome (MetS), the role of subcutaneous adipose tissue (SAT) has been unclear. DahlS.Z- Lepr fa / Lepr fa (DS/obese) rats, an animal model of MetS, develop adipocyte hypertrophy and inflammation to similar extents in SAT and VAT. We have now investigated the effects of salt loading and SAT removal on cardiac, renal, and VAT pathology in DS/obese rats. Methods DS/obese rats were subjected to surgical removal of inguinal SAT or sham surgery at 8 weeks of age. They were provided with a 0.3% NaCl solution as drinking water or water alone for 4 weeks from 9 weeks of age. Results Salt loading exacerbated hypertension, insulin resistance, as well as left ventricular (LV) hypertrophy, inflammation, fibrosis, and diastolic dysfunction in DS/obese rats. It also reduced both SAT and VAT mass but aggravated inflammation only in VAT. Although SAT removal did not affect LV hypertrophy in salt-loaded DS/obese rats, it attenuated hypertension, insulin resistance, and LV injury as well as restored fat mass and alleviated inflammation and the downregulation of adiponectin gene expression in VAT. In addition, whereas salt loading worsened renal injury as well as upregulated the expression of renin–angiotensin-aldosterone system-related genes in the kidney, these effects were suppressed by removal of SAT. Conclusions SAT removal attenuated salt-induced exacerbation of MetS and LV and renal pathology in DS/obese rats. These beneficial effects of SAT removal are likely attributable, at least in part, to inhibition of both VAT and systemic inflammation.

Phosphatidylinositol 3‐kinase (PI3K) signaling promotes the differentiation and proliferation of regulatory B (Breg) cells, and the lipid phosphatase phosphatase and tensin homolog deleted on chromosome 10 (PTEN) antagonizes the PI3K–Akt signaling pathway. We previously demonstrated that cardiac Akt activity is increased and that restraint stress exacerbates hypertension and both heart and adipose tissue (AT) inflammation in DS/obese rats, an animal model of metabolic syndrome (MetS). We here examined the effects of restraint stress and pharmacological inhibition of PTEN on heart and AT pathology in such rats. Nine‐week‐old animals were treated with the PTEN inhibitor bisperoxovanadium‐pic [bpV(pic)] or vehicle in the absence or presence of restraint stress for 4 weeks. BpV(pic) treatment had no effect on body weight or fat mass but attenuated hypertension in DS/obese rats subjected to restraint stress. BpV(pic) ameliorated left ventricular (LV) inflammation, fibrosis, and diastolic dysfunction as well as AT inflammation in the stressed rats. Restraint stress reduced myocardial capillary density, and this effect was prevented by bpV(pic). In addition, bpV(pic) increased the proportions of Breg and B‐1 cells as well as reduced those of CD8 + T and B‐2 cells in AT of stressed rats. Our results indicate that inhibition of PTEN by bpV(pic) alleviated heart and AT inflammation in stressed rats with MetS. These positive effects of bpV(pic) are likely due, at least in part, to a reduction in blood pressure, an increase in myocardial capillary formation, and an altered distribution of immune cells in fat tissue that result from the activation of PI3K–Akt signaling.

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