Objective Phosphatidylethanolamine (PtdEtn) is a major phospholipid in mammals. It is synthesized via two pathways, the CDP-ethanolamine pathway in the endoplasmic reticulum and the phosphatidylserine (PtdSer) decarboxylase (PSD) pathway in the mitochondria. While the CDP-ethanolamine pathway is considered the major route for PtdEtn synthesis in most mammalian tissues, little is known about the importance of the PSD pathway in vivo, especially in tissues enriched with mitochondria such as skeletal muscle. Therefore, we aimed to examine the role of the mitochondrial PSD pathway in regulating PtdEtn homeostasis in skeletal muscle in vivo . Methods To determine the functional significance of this pathway in skeletal muscle in vivo , an adeno-associated viral vector approach was employed to knockdown PSD expression in skeletal muscle of adult mice. Muscle lipid and metabolite profiling was performed using mass spectrometry. Results PSD knockdown disrupted muscle phospholipid homeostasis leading to an ∼25% reduction in PtdEtn and an ∼45% increase in PtdSer content. This was accompanied by the development of a severe myopathy, evident by a 40% loss in muscle mass as well as extensive myofiber damage as shown by increased DNA synthesis and central nucleation. In addition, PSD knockdown caused marked accumulation of abnormally appearing mitochondria that exhibited severely disrupted inner membrane integrity and reduced OXPHOS protein content. Conclusions The PSD pathway has a significant role in maintaining phospholipid homeostasis in adult skeletal muscle. Moreover, PSD is essential for maintenance of mitochondrial integrity and skeletal muscle mass.

Purpose To identify dietary patterns derived from protein, polyunsaturated fatty acids (PUFA) and vitamin D and examine associations with malnutrition, low muscle mass and sarcopenia in cancer survivors. Methods This cross-sectional study included cancer survivors (n = 2415) from the UK Biobank (age [mean ± SD] 59.7 ± 7.1 years; 60.7% female). The Oxford WebQ 24-h dietary assessment estimated food and nutrient intakes. Reduced rank regression derived dietary patterns (response variables: protein [g/kg/day], PUFA [g/day] and vitamin D [μg/day]). Adjusted logistic regression analysis examined associations between dietary patterns and malnutrition, low muscle mass and sarcopenia. Results Three dietary patterns were identified: (i) ‘high oily fish and nuts’, characterised by higher oily fish and nuts and seeds intake; (ii) ‘low oily fish’, characterised by lower oily fish intake and higher potato intake; and (iii) ‘meat and dairy’, characterised by higher intake of meat, poultry and dairy. Eighteen percent of participants were malnourished, 5% had low muscle mass and 6.5% had sarcopenia. Odds of being malnourished were significantly lower with adherence to a ‘high oily fish and nuts’ pattern (OR: 0.57; 95% CI: 0.50, 0.65) and ‘low oily fish’ pattern (OR: 0.81; 95% CI: 0.73, 0.90). The ‘meat and dairy’ pattern was not associated with malnutrition. No dietary patterns were associated with low muscle mass or sarcopenia. Conclusions Energy-rich dietary patterns were associated with lower odds of malnutrition in cancer survivors but did not influence muscle mass or sarcopenia risk. Implications for Cancer Survivors Better understanding of dietary patterns may improve cancer-related outcomes for cancer survivors.

Dietary patterns examine the combinations, types and quantities of foods consumed in the diet. Compared to individual nutrients, dietary patterns may be better associated with cancer-related malnutrition, low muscle mass and sarcopenia. This scoping review identified associations between dietary patterns, assessed using data-driven methods (i.e., statistical methods used to derive existing dietary patterns) and hypothesis-orientated methods (i.e., adherence to diet quality indices), and malnutrition, low muscle (lean) mass and sarcopenia. MEDLINE, Embase and CINAHL databases were searched up to September 2021. Of the 3341 studies identified, seven studies were eligible for review. Study designs included experimental (n = 5) and observational (n = 2), and people with prostate, ovarian and endometrial, bladder, breast, and gastrointestinal cancers. One study used data-driven methods to derive dietary patterns, finding adherence to a ‘fat and fish’ diet was associated with lower odds of low muscle mass. Two studies examined adherence to hypothesis-orientated methods including the Mediterranean Diet Adherence Screener and Healthy Eating Index 2010 and four studies used ‘non-traditional’ approaches to analyse dietary patterns. Hypothesis-orientated dietary patterns, developed to improve general health and prevent chronic disease, and ‘non-traditional’ dietary patterns demonstrated inconsistent effects on muscle (lean) mass. All studies investigated muscle (lean) mass, omitting malnutrition and sarcopenia as cancer-related outcomes. This scoping review highlights the limited research examining the effect of dietary patterns on cancer-related outcomes.

Up to 70% of people with lung cancer may be affected by cancer-related malnutrition or muscle loss, depending on treatment modality and disease stage. This narrative review explores recent studies on malnutrition and muscle loss as well as nutritional and multimodal interventions to treat these conditions in the context of the changing treatment landscape in lung cancer. Various types of interventions including individualized counselling, protein and other specific nutrient supplementation, as well as multimodal interventions to treat malnutrition and muscle loss have been investigated. Overall, individualized dietary counselling, increasing protein intake and supplementation with omega-3 fatty acids appear to be beneficial for some, albeit varying, patient outcomes. Multimodal interventions, generally including a nutrition and exercise component, show promising results, however the impact on patient outcomes are mixed. A key finding of this review is a lack of large, randomised trials to guide nutrition intervention specifically in people with lung cancer. Despite the high prevalence of malnutrition and muscle loss in people with lung cancer and the known adverse outcomes, current evidence for nutrition intervention is limited. A targeted effort is required to improve the quality of evidence for nutrition intervention in this population to provide support for clinicians to deliver effective nutrition care.

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