Fatty liver, oxidative stress, and mitochondrial dysfunction are key pathophysiological features of insulin resistance and obesity. Butyrate, produced by fermentation in the large intestine by gut microbiota, and its synthetic derivative, the N-(1-carbamoyl-2-phenyl-ethyl) butyramide, FBA, have been demonstrated to be protective against insulin resistance and fatty liver. Here, hepatic mitochondria were identified as the main target of the beneficial effect of both butyrate-based compounds in reverting insulin resistance and fat accumulation in diet-induced obese mice. In particular, butyrate and FBA improved respiratory capacity and fatty acid oxidation, activated the AMPK–acetyl-CoA carboxylase pathway, and promoted inefficient metabolism, as shown by the increase in proton leak. Both treatments consistently increased utilization of substrates, especially fatty acids, leading to the reduction of intracellular lipid accumulation and oxidative stress. Finally, the shift of the mitochondrial dynamic toward fusion by butyrate and FBA resulted in the improvement not only of mitochondrial cell energy metabolism but also of glucose homeostasis. In conclusion, butyrate and its more palatable synthetic derivative, FBA, modulating mitochondrial function, efficiency, and dynamics, can be considered a new therapeutic strategy to counteract obesity and insulin resistance.

Brain mitochondrial dysfunction is involved in the development of neurological and neurodegenerative diseases. Mitochondria specifically located at synapses play a key role in providing energy to support synaptic functions and plasticity, thus their defects may lead to synaptic failure, which is a common hallmark of neurodegenerative diseases. High-Fat Diet (HFD) consumption increases brain oxidative stress and impairs brain mitochondrial functions, although the underlying mechanisms are not completely understood. The aim of our study is to analyze neuroinflammation and mitochondrial dysfunctions in brain cortex and synaptosomal fraction isolated from a mouse model of diet-induced obesity. Male C57Bl/6 mice were divided into two groups fed a standard diet or HFD for 18 weeks. At the end of the treatment, inflammation (detected by ELISA), antioxidant state (measured by enzymatic activity), mitochondrial functions and efficiency (detected by oxidative capacity and Seahorse analysis), and brain-derived neurotrophic factor (BDNF) pathway (analyzed by western blot) were determined in brain cortex and synaptosomal fraction. In HFD animals, we observed an increase in inflammatory parameters and oxidative stress and a decrease in mitochondrial oxidative capacity both in the brain cortex and synaptosomal fraction. These alterations parallel with modulation of BDNF, a brain key signaling molecule that is linking synaptic plasticity and energy metabolism. Neuroinflammation HFD-dependent negatively affects BDNF pathway and mitochondrial activity in the brain cortex. The effect is even more pronounced in the synaptic region, where the impaired energy supply may have a negative impact on neuronal plasticity.

The gut microbiota plays a pivotal role in immune system development and function. Modification in the gut microbiota composition (dysbiosis) early in life is a critical factor affecting the development of food allergy. Many environmental factors including caesarean delivery, lack of breast milk, drugs, antiseptic agents, and a low-fiber/high-fat diet can induce gut microbiota dysbiosis, and have been associated with the occurrence of food allergy. New technologies and experimental tools have provided information regarding the importance of select bacteria on immune tolerance mechanisms. Short-chain fatty acids are crucial metabolic products of gut microbiota responsible for many protective effects against food allergy. These compounds are involved in epigenetic regulation of the immune system. These evidences provide a foundation for developing innovative strategies to prevent and treat food allergy. Here, we present an overview on the potential role of gut microbiota as the target of intervention against food allergy.

Milk contains several important nutrients that are beneficial for human health. This review considers the nutritional qualities of essential fatty acids (FAs), especially omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) present in milk from ruminant and non-ruminant species. In particular, the impact of milk fatty acids on metabolism is discussed, including its effects on the central nervous system. In addition, we presented data indicating how animal feeding—the main way to modify milk fat composition—may have a potential impact on human health, and how rearing and feeding systems strongly affect milk quality within the same animal species. Finally, we have presented the results of in vivo studies aimed at supporting the beneficial effects of milk FA intake in animal models, and the factors limiting their transferability to humans were discussed.

Obesity is a major risk factor for several metabolic diseases, including type 2 diabetes, hyperlipidemia, cardiovascular diseases, and brain disorders. Growing evidence suggests the importance of inter-organ metabolic communication for the progression of obesity and the subsequent onset of related disorders. This review provides a broad overview of the pathophysiological processes that from adipose tissue dysfunction leading to altered multi-tissue crosstalk relevant to regulating energy homeostasis and the etiology of obesity. First, a comprehensive description of the role of adipose tissue was reported. Then, attention was turned toward the unhealthy expansion of adipose tissue, low-grade inflammatory state, metabolic inflexibility, and mitochondrial dysfunction as root causes of systemic metabolic alterations. In addition, a short spot was devoted to iron deficiency in obese conditions and the role of the hepcidin–ferroportin relationship in the management of this issue. Finally, different classes of bioactive food components were described with a perspective to enhance their potential preventive and therapeutic use against obesity-related diseases.