Macronutrients and the Adipose-Liver Axis in Obesity and Fatty Liver

Abstract

Macronutrient metabolism is a highly orchestrated process, with adipose tissue and liver each playing central roles in nutrient uptake, processing, transport, and storage. These 2 tissues form an important metabolic circuit, particularly as it relates to lipids as the primary storage form of excess energy. The function of the circuit is influenced by many factors, including the quantity and type of nutrients consumed and their impact on the overall health of the tissues. In this review we begin with a brief summary of the homeostatic disposition of lipids between adipose tissue and liver and how these processes can become dysregulated in obesity. We then explore how specific dietary nutrients and nutrient combinations can exert unique influences on the liver-adipose tissue axis.

Keywords: Carbohydrate; Diet; Fat; Fatty Liver Disease; Metabolism.

Figure 1

Route of dietary carbohydrates and fats to the liver and adipose tissue. Dietary carbohydrate enters the portal circulation from the intestine and enters the liver. Excess substrate not needed for metabolism is converted to fatty acid via DNL and incorporated into triglyceride. Triglycerides are exported from the liver as VLDL, where they are delivered to adipose tissue, where they are broken down into FFA by the enzyme LPL and stored. Dietary fat is packaged into chylomicrons in the intestine and delivered initially to muscle and adipose tissue. Any lipid remaining in the chylomicron remnants are routed to the liver, as are “spillover” FFA not taken up by adipocytes. CHO, carbohydrate; TG, triglyceride.

Figure 2

Endocrine interactions between liver and adipose tissue and the influence of macronutrients. Under conditions of dietary excess/obesity, adipose tissue adiponectin production declines and several proinflammatory cytokines and chemokines are upregulated. This can promote inflammation and insulin resistance in both tissues. FGF21 is upregulated in the liver, but its action is inhibited, preventing energy expenditure in adipose tissue and promoting lipolysis. The general contribution of individual macronutrients to the dysfunction of adipose tissue and liver in obesity and NAFLD is shown schematically (see text for details). CHO, carbohydrate; IL, interleukin; TNF, tumor necrosis factor.