Hepatokines are recently identified proteins that exert systemic metabolic effects in an endocrine-like manner.  These proteins impact insulin sensitivity and glucose metabolism, making them potential targets for the management of obesity-related diseases.  Chronic energy status and metabolic disease impact hepatokines, including fibroblast growth factor 21 (FGF21), leukocyte cell-derived chemotaxin 2 (LECT2), fetuin-A, fetuin-B, and selenoprotein P (SeP).  The growing literature using cell culture and animal models of disease suggest that hepatokines are sensitive to acute nutritional effects, but human data does not exist.  Willis and colleagues addressed this void in our understanding and published a report of their findings in the May 2020 issue of The Journal of Nutrition.

Healthy men (n=12) participated in a randomized, crossover design study in which they consumed a control diet (36% total energy as fat) or a hyperenergetic, high-fat diet (65% total energy as fat).  The diet periods were 7 days long and were separated by 3 weeks.  Insulin sensitivity was assessed before and after each diet period, and plasma concentrations of hepatokines were determined on days 1, 3, and 7 of each diet period.

The hyperenergetic, high fat diet caused an increase in FGF21 on days 1 and 3, LECT2 on days 3 and 7, and fetuin-A on day 7.  However, fetuin-B and SeP were not impacted by the hyperenergetic, high fat diet.  The data led the authors to conclude that an acute period of high-fat, hyperenergetic meals impacts certain hepatokines in healthy men in a time-dependent manner. 

In a commentary on this article, Gonzalez notes the important differences in the extent of increases in the circulating hepatokines and the time courses during which the increases were observed.  These patterns in the responses suggest they are differentially regulated.  Moreover, he points out that it is difficult to discern whether the changes were the result of elevated energy intake or specifically due to elevated fat intake.  Gonzalez also recommends further work that would explore how the responses may be impacted by physical activity, and to establish links between nutrient storage and hepatokine secretion.

References Willis SA, Sargeant JA, Yates T, Takamura T, Takayama H, Gupta V, Brittain E, Crawford J, Parry SA, Thackray AE, Varela-Mato V, Stensel DJ, Woods RM, Hulston CJ, Aithal GP, King JA. Acute hyperenergetic, high-fat feeding increases circulating FGF21, LECT2, and Fetuin-A in health men. The Journal of Nutrition, Volume 150, Issue 5, May 2020, Pages 1076–1085, DOI: https://doi.org/10.1093/jn/nxz333.

Gonzalez JT. Early hepatic signals of fat overload.  The Journal of Nutrition, Volume 150, Issue 5, May 2020, Pages 977–978, DOI: https://doi.org/10.1093/jn/nxaa012.

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