Skeletal muscle is a major organ of insulin-induced glucose metabolism. In addition, loss of muscle mass is closely linked to insulin resistance (IR) and metabolic syndrome (Met-S). Skeletal muscle loss and accumulation of intramuscular fat are associated with a variety of pathologies through a combination of factors, including oxidative stress, inflammatory cytokines, mitochondrial dysfunction, IR, and inactivity. Sarcopenia, defined by a loss of muscle mass and a decline in muscle quality and muscle function, is common in the elderly and is also often seen in patients with acute or chronic muscle-wasting diseases. The relationship between Met-S and sarcopenia has been attracting a great deal of attention these days. Persistent inflammation, fat deposition, and IR are thought to play a complex role in the association between Met-S and sarcopenia. Met-S and sarcopenia adversely affect QOL and contribute to increased frailty, weakness, dependence, and morbidity and mortality. Patients with Met-S and sarcopenia at the same time have a higher risk of several adverse health events than those with either Met-S or sarcopenia. Met-S can also be associated with sarcopenic obesity. In this review, the relationship between Met-S and sarcopenia will be outlined from the viewpoints of molecular mechanism and clinical impact.

The term “cachexia” is derived from the Greek words kakos (bad) and hexis (habit). Cachexia is a malnutrition associated with chronic diseases such as cancer, chronic heart failure, chronic renal failure, and autoimmune diseases, and is characterized by decreased skeletal muscle mass. Cancer cachexia is quite common in patients with advanced cancer. Weight loss is also a characteristic symptom of cancer cachexia, along with decreased skeletal muscle mass. As nutritional supplementation alone cannot improve cachexia, cytokines and tumor-derived substances have been attracting attention as its relevant factors. Cancer cachexia can be also associated with reduced chemotherapeutic effects, increased side effects and treatment interruptions, and even poorer survival. In 2011, a consensus definition of cachexia has been proposed, and the number of relevant research reports has increased significantly. However, the pathogenesis of cachexia is not fully understood, and there are currently few regulatory-approved standard treatments for cachexia. The main reason for this is that multiple etiologies are involved in the development of cachexia. In this review, we will outline the current status of cachexia, the mechanisms of which have been elucidated in recent years, especially from the perspective of advanced cancer.

Malnutrition is a major contributor to muscle loss and muscle dysfunction, known as sarcopenia. Malnutrition is common in patients with inflammatory bowel disease (IBD). IBD includes ulcerative colitis (UC) and Crohn’s disease (CD). The number of patients with IBD has recently been increasing. More severe malnutrition is often seen in CD compared to UC, probably due to CD affecting the main site of nutrient absorption, extensive mucosal lesions, fistulas, short bowel syndrome after resection, or obstruction of the gastrointestinal tract. A recent meta-analysis showed the high prevalence of sarcopenia in patients with IBD, and thus sarcopenia is a very important problem for IBD. Although IBD is more common in younger patients, sarcopenia can develop through a variety of mechanisms, including malnutrition, chronic inflammation, increased inflammatory status in adipose tissue, vitamin deficiency, and imbalance of the muscle–gut axis. In addition, sarcopenia has a negative impact on postoperative complications and hospital stay in patients with IBD. Appropriate intervention for sarcopenia may be important, in addition to clinical remission and endoscopic mucosal healing in patients with IBD. Much more attention will thus be paid to sarcopenia in patients with IBD. In this review, we outline IBD and sarcopenia, based on the current evidence.

Zinc is an essential trace element for the maintenance of life because it acts as a center of activity or cofactor for hundreds of enzymes. Zinc deficiency causes a variety of symptoms, including anemia, dermatitis, stomatitis, alopecia, bedsores, decreased appetite, impaired growth, gonadal dysfunction, susceptibility to infection, and taste disorders, etc. In March 2017, zinc acetate hydrate, which had been approved for Wilson disease in Japan, received an additional indication for hypozincemia. Hypozincemia is frequently observed in patients with chronic liver disease (CLD), especially cirrhosis, and it has recently been shown that hypozincemia is closely related to the development of liver fibrosis and increased risk of liver carcinogenesis, in addition to the appearance of various subjective symptoms. Moreover, hypozincemia in CLD may be associated with sarcopenia (i.e., decrease in muscle strength and muscle mass) and frailty (i.e., vulnerability), which receive much attention these days. It is assumed that treatment with zinc acetate hydrate will become widespread in patients with CLD. Zinc acetate hydrate may also have potential for improving sarcopenia in patients with CLD. This review primarily outlines the significance of zinc in patients with CLD.

Anti-programmed cell death-1 (PD-1) antibodies has been approved to treat HCC. Some PD-1 ligands (PD–L1 and PD–L2) negative tumors respond to treatment of anti-PD-1 antibodies, and this fact may be caused by the expression of PD-1 ligands on non-tumor cells. PD–L1 was recently found to be expressed on CD14⁺ cells from cancer patients. We investigate PD-1 ligands expression on CD14⁺ cells of patients with HCC and the role of CD14⁺ cells in an antitumor response. In this study, 87 patients diagnosed with HCC were enrolled. CD14⁺ cells from patients with HCC expressed PD–L1 (4.5–95.5%) and PD–L2 (0.2–95.0%). According to cut-off values, we classified patients as those either with PD–L1⁺PD–L2⁺CD14⁺ cells or other types of CD14⁺ cells. The overall survival of patients with PD–L1⁺PD–L2⁺CD14⁺ cells was shorter than that of patients with other types of CD14⁺ cells (p = 0.0023). PD–L1⁺PD–L2⁺CD14⁺ cells produced IL-10 and CCL1, and showed little tumoricidal activity against HepG2 cells. The tumoricidal activity of CD8⁺ cells from patients with PD–L1⁺PD–L2⁺CD14⁺ cells were suppressed by co-cultivation with CD14⁺ cells from the syngeneic patient. Furthermore, anti-PD-1 antibody restored their tumoricidal activity of CD8⁺ cells. In conclusion, some patients with HCC have PD–L1⁺PD–L2⁺CD14⁺ cells that suppress their antitumor response. These inhibitory functions of CD14⁺ cells may be associated with a poor prognosis in these patients.