The ketogenic diet (KD) is characterized by minimal carbohydrate, moderate protein, and high fat intake, leading to ketosis. It is recognized for its efficiency in weight loss, metabolic health improvement, and various therapeutic interventions. The KD enhances glucose and lipid metabolism, reducing triglycerides and total cholesterol while increasing high-density lipoprotein levels and alleviating dyslipidemia. It significantly influences adipose tissue hormones, key contributors to systemic metabolism. Brown adipose tissue, essential for thermogenesis and lipid combustion, encounters modified UCP1 levels due to dietary factors, including the KD. UCP1 generates heat by uncoupling electron transport during ATP synthesis. Browning of the white adipose tissue elevates UCP1 levels in both white and brown adipose tissues, a phenomenon encouraged by the KD. Ketone oxidation depletes intermediates in the Krebs cycle, requiring anaplerotic substances, including glucose, glycogen, or amino acids, for metabolic efficiency. Methylation is essential in adipogenesis and the body’s dietary responses, with DNA methylation of several genes linked to weight loss and ketosis. The KD stimulates FGF21, influencing metabolic stability via the UCP1 pathways. The KD induces a reduction in muscle mass, potentially involving anti-lipolytic effects and attenuating proteolysis in skeletal muscles. Additionally, the KD contributes to neuroprotection, possesses anti-inflammatory properties, and alters epigenetics. This review encapsulates the metabolic effects and signaling induced by the KD in adipose tissue and major metabolic organs.

Metformin, the most commonly used drug for type 2 diabetes, has recently been shown to have beneficial effects in patients with cancer. Despite growing evidence that metformin can inhibit tumor cell proliferation, invasion, and metastasis, studies on drug resistance and its side effects are lacking. Here, we aimed to establish metformin-resistant A549 human lung cancer cells (A549-R) to determine the side effects of metformin resistance. Toward this, we established A549-R by way of prolonged treatment with metformin and examined the changes in gene expression, cell migration, cell cycle, and mitochondrial fragmentation. Metformin resistance is associated with increased G1-phase cell cycle arrest and impaired mitochondrial fragmentation in A549 cells. We demonstrated that metformin resistance highly increased the expression of proinflammatory and invasive genes, including BMP5, CXCL3, VCAM1, and POSTN, using RNA-seq analysis. A549-R exhibited increased cell migration and focal adhesion formation, suggesting that metformin resistance may potentially lead to metastasis during anti-cancer therapy with metformin. Taken together, our findings indicate that metformin resistance may lead to invasion in lung cancer cells.

Chitosan, poly[β-(1–4)-linked-2-amino-2-deoxy-d-glucose], is a polysaccharide with broad applications in various biomaterial and biomedical fields, primarily because of its nontoxicity. Because the biodegradable biopolymer chitosan can be catalyzed by the alkaline partial deacetylation of chitin in shrimp and crab shells, its degree of deacetylation is crucial for proper application. However, the antiviral properties of deacetylated chitosan in combination with other compounds remain unclear. We used a plaque assay to examine the antiviral activity of deacetylated chitosan against human influenza A virus (H1N1) and parainfluenza virus type 3 (HPIV3) when supplemented with grapefruit seed extract (GSE). We demonstrated that deacetylated chitosan reduced H1N1- and HPIV3-induced plaque formation in Madin–Darby canine kidney (MDCK) cells. Chitosan also decreased viral RNA expression in H1N1- and HPIV3-infected A549 cells. Furthermore, antiviral activity analysis in human A549 cells revealed that deacetylated chitosan prevented virus-induced p38 MAPK activation and mitochondrial fragmentation. These findings indicate that deacetylated chitosan with GSE may be a promising antiviral biomaterial against influenza and parainfluenza viruses.