Necroptosis contributes to hepatocyte death in nonalcoholic steatohepatitis (NASH), but the fate and roles of necroptotic hepatocytes (necHCs) in NASH remain unknown. We show here that the accumulation of necHCs in human and mouse NASH liver is associated with an up-regulation of the “don’t-eat-me” ligand CD47 on necHCs, but not on apoptotic hepatocytes, and an increase in the CD47 receptor SIRPα on liver macrophages, consistent with impaired macrophage-mediated clearance of necHCs. In vitro, necHC clearance by primary liver macrophages was enhanced by treatment with either anti-CD47 or anti-SIRPα. In a proof-of-concept mouse model of inducible hepatocyte necroptosis, anti-CD47 antibody treatment increased necHC uptake by liver macrophages and inhibited markers of hepatic stellate cell (HSC) activation, which is responsible for liver fibrogenesis. Treatment of two mouse models of diet-induced NASH with anti-CD47, anti-SIRPα, or AAV8-H1-shCD47 to silence CD47 in hepatocytes increased the uptake of necHC by liver macrophages and decreased markers of HSC activation and liver fibrosis. Anti-SIRPα treatment avoided the adverse effect of anemia found in anti-CD47–treated mice. These findings provide evidence that impaired clearance of necHCs by liver macrophages due to CD47-SIRPα up-regulation contributes to fibrotic NASH, and suggest therapeutic blockade of the CD47-SIRPα axis as a strategy to decrease the accumulation of necHCs in NASH liver and dampen the progression of hepatic fibrosis.

Curcumin, a naturally occurring plant polyphenolic compound, may have beneficial effects in nonalcoholic steatohepatitis (NASH) development. We examined whether curcumin supplementation could be used in both prevention and treatment of NASH with fibrosis. Female Wistar rats were provided ad libitum access to a “western diet” (WD) high in fat (43% kcal), sucrose (29% kcal), and cholesterol (2% w/v), as well as 15% fructose drinking water. Intraperitoneal CC1₄ injections (0.5 mL/kg) were also administered at weeks 1, 2, 4, and 6 to accelerate development of a NASH with fibrosis phenotype. Rats were randomized to four groups (n = 9–12/group) and fed ad libitum: (1) WD for 8‐weeks (8WD), (2) WD enriched with curcumin for 8‐weeks (8WD+C; 0.2% curcumin, BCM‐95, DolCas Biotech) to assess prevention, (3) WD for 12‐weeks (12WD), (4) WD for 8‐weeks followed by 4‐weeks WD+C (12WD+C) to assess treatment. Curcumin prevention (8WD vs. 8WD+C) attenuated (P < 0.05) histological liver inflammation, molecular markers of fibrosis (Col1a1 mRNA) and a serum marker of liver injury (AST). Curcumin treatment (12WD vs. 12WD+C) reduced (P < 0.05) hepatocellular inflammation, steatosis, NAFLD Activity Scores, and serum markers of liver injury (AST, ALP). Moreover, curcumin treatment also increased hepatic pACC/ACC, ApoB100, and SOD1 protein, and decreased hepatic FGF‐21 levels; whereas, curcumin prevention increased hepatic glutathione levels. Both curcumin prevention and treatment reduced molecular markers of hepatic fibrosis (Col1a1 mRNA) and inflammation (TNF‐α, SPP1 mRNA). Curcumin supplementation beneficially altered the NASH phenotype in female Wistar rats, particularly the reversal of hepatocellular inflammation.

Dance has been explored as a therapeutic intervention because of its unique combination of exercise, music and cognitive engagement. Dance therapy is a specific form of dance-based treatment that focuses on how movement correlates with psychological aspects such as self-awareness, expression and coordination, which culminate in a mind–body treatment. In recent years, dance-based programmes have been used as an intervention to improve symptoms of neurological diseases/disorders. Positive results have been shown for patients suffering from Parkinson’s disease, dementia and depression. The neurological adaptations such as improved neural activity and neurogenesis are induced by the combination of coordinated movement strategies, exercise, musical arrangements and social interactions (partnering). With the continued growth of dance therapy, the purpose of this review is to explain the recently proposed theories of how neural changes are mediated through dance, and discuss the positive effects on those suffering from neurological disorders.

Ketogenic diets (KDs) are shown to benefit hepatic metabolism; however, their effect on the liver when combined with exercise is unknown. We investigated the effects of a KD versus a “western” diet (WD) on markers of hepatic lipid metabolism and oxidative stress in exercising rats. Male and female Wistar rats with access to voluntary running wheels were randomized to 3 groups (n = 8–14 per group): standard chow (SC; 17% fat), WD (42% fat), or KD (90.5% fat) for 7 weeks. Body fat percentage (BF%) was increased in WD and KD versus SC, although KD females displayed lower BF% versus WD (p ≤ 0.05). Liver triglycerides were higher in KD and WD versus SC but were attenuated in KD females versus WD (p ≤ 0.05). KD suppressed hepatic markers of de novo lipogenesis (fatty acid synthase, acetyl coenzyme A carboxylase) and increased markers of mitochondrial biogenesis/content (peroxisome proliferator activated receptor-1α, mitochondrial transcription factor A (TFAM), and citrate synthase activity). KD also increased hepatic glutathione peroxidase 1 and lowered oxidized glutathione. Female rats exhibited elevated hepatic markers of mitochondrial biogenesis (TFAM), mitophagy (light chain 3 II/I ratio, autophagy-related protein 12:5), and cellular energy homeostasis (phosphorylated 5′AMP-activated protein kinase/5′AMP-activated protein kinase) versus males. These data highlight that KD and exercise beneficially impacts hepatic metabolism and oxidative stress and merits further investigation. Novelty KD feeding combined with exercise improved hepatic oxidative stress, suppressed markers of de novo lipogenesis, and increased markers of mitochondrial content versus WD feeding. Males and females responded similarly to combined KD feeding and exercise. Female rats exhibited elevated hepatic markers of autophagy/mitophagy and energy homeostasis compared with male rats.

Introduction: Cardiac rehabilitation (CR) is a primary prescribed treatment for a variety of cardiovascular disease states, including: coronary artery disease, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), myocardial infarction (MI), and heart failure. For this reason, exercise prescription guidelines for cardiac patients have been established. However, it is unclear how these guidelines are being administered at cardiac rehabilitation centers. The purpose of this study is to assess current exercise prescription techniques at cardiac rehabilitation clinics across several Midwest states in the United States. Methods: Fifty-eight CR programs from Michigan, Indiana, Illinois, Minnesota, Wisconsin, and Ohio were administered a questionnaire assessing clinic characteristics, aerobic and resistance exercise prescription techniques. Results: Most reported patient types were PCI, CABG, and MI. Clinical exercise physiologists were the primary exercise prescription writers (81%). Only 32% of the clinics required a clinical certification. Baseline stress tests prior to CR were performed in 33% of programs. Rating of Perceived Exertion (RPE) was the most commonly used indicator of exercise intensity, followed by heart rate reserve (HRR), and METs. Resistance exercise was practiced in 89% of CR programs. The most common intensity indicator was trial and error, and RPE. Conclusion: Results demonstrate exercise prescription variability among CR programs. This emphasizes the complexity and expertise among clinical exercise physiologists. These results also highlight the importance that academic programs place on training students across all prescription techniques, and utilization of research-based prescription guidelines published by professional organizations.