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Calorie restriction (1) reduces adipokine release which attenuates systemic inflammatory signaling (401), (2) reduces serum lipids and comorbidities associated with disease exacerbation (e.g., hypertension) (400), (3) activates autophagy, which protects against hepatic steatosis and inflammation (402), and (4) activates various molecular pathways (e.g., AMPK) which are associated with protection against NASH and atherosclerosis (403, 404)

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Following this sensor is a stretch of HEAT repeats that also bind the substrate (Figs