Carbohydrates can be converted into fatty acids via de novo lipogenesis (DNL). Although DNL is considered inefficient, these endogenous fatty acids contribute substantially to the esterification pathway in adipose tissue, together with fatty acids of feeding. This article revisited the concepts of DNL and aimed to discuss the clinical magnitude of carbohydrate overfeeding and fat mass accumulation. Although fat storage resulting from fat intake is more favorable for fat mass accrual than carbohydrates due to molecule structure and metabolism (e.g., oxidation and thermic effect), carbohydrates can substantially participate in lipogenesis and esterification under excess carbohydrate intake over time. Regarding only monosaccharide overfeeding, glucose and fructose favor the subcutaneous and visceral adipose tissue, respectively. While fructose and sucrose are considered villains in nonalcoholic fatty liver disease, energy surplus from carbohydrates, regardless of sources, can be considered an underlying cause of obesity. Interestingly, some degree of DNL in adipocytes may be favorable to mitigate a high deposition of fatty acids in the liver, conferring a physiological role. Although "fat burns in the flame of carbohydrate" is a praiseworthy phrase that has helped describe basic concepts in biochemistry for many decades, it appears to be overvalued and extrapolated even nowadays. DNL cannot be neglected. It is time to consider DNL an efficient biochemical process in health and disease.
Keywords: Fat mass; Fructose; Glucose; High-carbohydrate diet; Obesity; de novo lipogenesis.
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