Long term intake of barley beta-D-glucan attenuates glucose intolerance, mood disorders and cognitive decline in high-fat diet-induced obese mice exposed to chronic psychosocial stress

High-fat diet (HFD)-induced obesity causes insulin resistance and increases vulnerability to chronic psychosocial stress-induced dysfunctions, including anxiety and mood disorders, cognitive decline and myocardial ischemia. The inhibition of class I histone deacetylases leads to metabolic homeostasis and dietary barley (1.3) beta-D-glucan (β-D-glucan), a water-soluble polysaccharide, increases levels of histone H4 acetylation. We tested whether the long-term intake of β-D-glucan prevents glucose intolerance, affective disorders and cognitive decline in stressed obese mice. 24 male mice C57BL/6 were fed three different diets for 18 wks: 1) standard diet (SD; 10% Kcal from fat; n=8), 2) HFD (58% Kcal from fat; n=8) or 3) HFD supplemented with 3% w/v β-D-glucan (HFD+BG; 58% Kcal from fat; n=8). From the 16th to the 18th wk all animals underwent to the resident-intruder stress test. Before and after chronic stress, the anxiety-related behaviour and the spatial working memory were evaluated by elevated plus-maze (PM; entries in open arms, %) and Y-maze test (YM; spontaneous alternation, %). At the end of the experiment, plasma brain derived neurotrophic factor (BDNF) and the hippocampal expression of tropomyosin-related kinase B (TrKB, the BDNF receptor) were evaluated because of their key role in energy balance and in the pathogenesis of affective and cognitive disorders. At the 16th wk, HFD’s body weight was increased compared to SD group (+36.6%, p<0.01), but the β-D-glucan supplementation prevented the HFD-induced weight gain. The glucose tolerance test area under the curve (AUC; 0–120 min) was higher in HFD than SD mice fasted (447.7 ± 55 vs 259.1 ± 23.4 mg/dL*min: p<0.001); although, it was lower (−25.8%, p<0.01) in the HFD+BG compared to HFD group. Compared to SD group, open arm activity at the16th week was lower in the HFD (−250%, p<0.001) than in the HFD+BG group (−55.5% p<0.05). After stress, the entries in open arms were absent in HFD mice and were further reduced (−75%, p<0.01) in SD animals, yet the open arm activity was unchanged in HFD+BG group. Spatial working memory after 16 wks. was similar in all groups, but after stress it was reduced only in HFD mice (−18.9%, p<0.01). Compared to SD, reduction of BDNF plasma levels was detected in HFD mice, but not in HFD+BG group (SD, 66 ± 22 pg/ml; HFD, 27 ± 11 pg/ml; HFD+BG, 78 ± 32 pg/ml, p<0.05). The hippocampal expression of TrKB in HFD+BG group was significantly higher than HFD mice (HFD+BG, 0.63 ± 0.13 a.u.; SD, 0.5± 0.1 a.u.; HFD, 0.44 ± 0.05 a.u., p<0.05). In conclusion, β-D-glucan intake attenuates glucose intolerance and improves the stress-induced response in obese mice through the upregulation of hippocampal BDNF/TrkB pathway. Our data provide a basis for developing a new nutraceutical approach for the protection against obesity/stress-related disorders.