The latest studies have indicated a strong relationship between systemic insulin resistance (IR) and higher incidence of neurodegeneration, dementia, and mild cognitive impairment. Although some of these abnormalities could be explained by chronic hyperglycaemia, hyperinsulinemia, dyslipidaemia, and/or prolonged whole-body inflammation, the key role is attributed to the neuronal redox imbalance and oxidative damage. In this mini review, we provide a schematic overview of intracellular oxidative stress and mitochondrial abnormalities in the IR brain. We highlight important correlations found so far between brain oxidative stress, ceramide generation, β-amyloid accumulation, as well as neuronal apoptosis in the IR conditions.

Oxidative stress is a key pathogenic factor in both neurogenerative and metabolic diseases. However, its contribution in the brain complications of insulin resistance is still not well understood. Therefore, the aim of this study was the evaluation of redox homeostasis and oxidative damage in the hypothalamus and cerebral cortex of insulin‐resistant and control rats. 16 male Wistar rats were divided into two equal groups (n = 8): the control and high fat diet group (HFD). Prooxidant enzymes (xanthine oxidase and NADPH oxidase); enzymatic and nonenzymatic antioxidants [glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase‐1 (SOD‐1), and uric acid (UA)]; and oxidative damage products [advanced glycation end products (AGE), 4‐hydroxynonenal (4‐HNE), malondialdehyde (MDA), and 8‐hydroxy‐2 ^′‐deoxyguanosine (8‐OHdG)] as well as the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), and total ferric reducing ability of sample (FRAP) were evaluated in the hypothalamus and cerebral cortex as well as serum/plasma of HFD‐fed and control rats. The activity of prooxidant enzymes was significantly increased in the cerebral cortex and hypothalamus of HFD‐fed rats vs. control rats. Additionally, we have showed enhanced antioxidant efficiency in the hypothalamus (↑CAT, ↑UA, ↑TAC, and ↑FRAP) and cerebral cortex (↑GPx, ↑CAT, ↑SOD‐1, ↑UA, ↑TAC, and ↑FRAP) of HFD‐fed rats. All of the oxidative damage markers (AGE, 4‐HNE, MDA, 8‐OHdG, and OSI) were significantly increased in the cerebral cortex of insulin‐resistant rats, while only 4‐HNE and MDA were markedly higher in the hypothalamus of the HFD group. Summarizing, the results of our study indicate an adaptive brain response to the increased production of free radicals under insulin resistance conditions. Despite the increase in antioxidative defense systems, this mechanism does not protect both brain structures from oxidative damages. However, the cerebral cortex is more susceptible to oxidative stress caused by HFD.

This is the first study to analyze the impact of high protein diet (HPD) on antioxidant defense, redox status, as well as oxidative damage on both a local and systemic level. Male Wistar rats were divided into two equal groups (n = 9): HPD (44% protein) and standard diet (CON; 24.2% protein). After eight weeks, glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase-1 (SOD-1), reduced glutathione (GSH), uric acid (UA), total antioxidant (TAC)/oxidant status (TOS) as well as advanced glycation end products (AGE), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were analyzed in the serum/plasma, cerebral cortex, and hypothalamus of HPD and CON rats. HPD resulted in higher UA concentration and activity of GPx and CAT in the hypothalamus, whereas in the cerebral cortex these parameters remained unchanged. A significantly lower GSH content was demonstrated in the plasma and hypothalamus of HPD rats when compared to CON rats. Both brain structures expressed higher content of 4-HNE and MDA, whereas AGE was increased only in the hypothalamus of HPD animals. Despite the enhancement in antioxidant defense in the hypothalamus, this mechanism does not protect the hypothalamus from oxidative damage in rats. Hypothalamus is more susceptible to oxidative stress caused by HPD.

Branched chain amino acids (BCAA) and their derivatives are bioactive molecules with pleiotropic functions in the human body. Elevated fasting blood BCAA concentrations are considered as a metabolic hallmark of obesity, insulin resistance, dyslipidaemia, nonalcoholic fatty liver disease, type 2 diabetes and cardiovascular disease. However, since increased BCAA amount is observed both in metabolically healthy and obese subjects, a question whether BCAA are mechanistic drivers of insulin resistance and its morbidities or only markers of metabolic dysregulation, still remains open. The beneficial effects of BCAA on body weight and composition, aerobic capacity, insulin secretion and sensitivity demand high catabolic potential toward amino acids and/or adequate BCAA intake. On the opposite, BCAA-related inhibition of lipogenesis and lipolysis enhancement may preclude impairment in insulin sensitivity. Thereby, the following review addresses various strategies pertaining to the modulation of BCAA catabolism and the possible roles of BCAA in energy homeostasis. We also aim to elucidate mechanisms behind the heterogeneity of ramifications associated with BCAA modulation.

Kowal K, et al. Allergy Asthma Immunol Res. 2019 May;11(3):330-342. https://doi.org/10.4168/aair.2019.11.3.330

The effects of phosphate deficiency on the plant growth and acid phosphatase activity in two wheat cultivars (Triticum aestivum L. cv. ‘Bryza’ and ‘Opatka’) were studied. Pi content decreased significantly in the shoots and roots of all plants grown for one to three weeks in the nutrient medium without phosphate (−P). Phosphate starvation affected growth of both wheat cultivars in a similar way: significantly decreased shoot and root mass, especially after three weeks growth on −P medium, even up to 8–11% of control. However the ratio of root/shoot fresh weight of −P plants increased (2–3 times more than control). The shoot height of −P wheat plants decreased to about 50–60% of the control after two to three weeks of culture; less affected by Pi deficiency was root elongation—no significant changes were observed for both wheat cultivars during one to three weeks of culture. Phosphate deficiency increased the activity of extracellular and intracellular acid phosphatases in comparison to phosphate-sufficient plants. The increase of intracellular acid phosphatase activity in leaves and roots was generally more significant in ‘Bryza’ cultivar as compared to ‘Opatka’, especially after two to three weeks of growth on −P medium. The increase of root surface acid phosphatase activity was the highest for Pi-deficient wheat cv. ‘Bryza’, after three weeks of culture in the −P medium. Generally, the increase of activity of acid phosphatases secreted by the roots of −P wheat plants was higher than those of intracellular acid phosphatases. These results indicate an important role of acid phosphatases in the acclimation of both wheat cultivars to early Pi deficiency.