The role of breakfast in adipose tissue biology

Adipose tissue has traditionally been viewed as an energy sink that can store excess calories in the form of triglycerides and then release non‐esterified fatty acids (NEFAs) and glycerol into the blood circulation during lipolysis of triglycerides. Since the discoveries of adipokines in the early 1990s, adipose tissue has also started to become recognized as an active endocrine organ that can affect cellular metabolic pathways at the systemic level (Scherer, 2016). Data obtained from studies conducted in genetically engineered mouse models have shed light on the extraordinary capability of adipose tissue to regulate systemic and adaptive metabolic responses to various nutritional changes (Scherer, 2016). Consistent with animal data, accumulating evidence has suggested that human adipose tissue is also dynamically changed in response to the alterations in dietary inputs and these metabolic adaptations in adipose tissue are associated with the alterations in whole‐body metabolism. For example, overfeeding and dietary restriction result in marked alterations in adipose tissue mass, adipose tissue expression of numerous biological pathways and genes involved in NEFA metabolism, and multi‐organ insulin sensitivity in people with obesity (Fabbrini et al. 2015; Magkos et al. 2016). These findings support the notion that adipose tissue biology could be critically involved in regulating adaptive metabolic responses in people.

In this issue of The Journal of Physiology, Gonzalez and colleagues investigated molecular responses of adipose tissue to prolonged morning fasting induced by skipping breakfast, which is a common practice in today's busy society (Gonzalez et al. 2018). The same group had previously conducted a randomized‐controlled trial (the Bath Breakfast Project) and evaluated the effects of 6 weeks of prolonged morning fasting (skip breakfast, 0 kcal intake until 12.00 h) and daily breakfast consumption (≥700 kcal intake before 11.00 h) on key metabolic function in people who are lean and obese (Betts et al. 2014; Chowdhury et al. 2016). In the present study, they analysed abdominal subcutaneous adipose tissue biopsy samples obtained before and after each intervention (Gonzalez et al. 2018). First, the authors found that prolonged morning fasting increased adipose tissue expression of several NEFA metabolism‐related genes, including ACADM (acyl‐coenzyme A dehydrogenase), a key enzyme involved in NEFA oxidation, in people who are lean, but not in those who are obese. These findings indicate that in lean individuals mitochondria could have a greater capability to handle excess lipids during fasting, compared to those in obese individuals. These molecular adaptations could be protective mechanisms of adipose tissue against metabolic stress induced by prolonged fasting in lean people. They also found morning fasting increased adipose tissue gene expression of IRS2 (insulin receptor substrate 2), a key component of proximal insulin signalling cascade, in both lean and obese groups. However, morning fasting did not change the adipose tissue gene expression of other insulin signalling components and it did not affect the protein contents of the insulin‐responsive glucose transporter 4 (GLUT4) and AKT1/2 compared to regular breakfast consumption. In addition, data obtained from in vitro studies conducted in primary adipocytes isolated from adipose tissue biopsies did not reveal any significant differences in insulin‐stimulated AKT phosphorylation on serine 473 between groups. The same authors previously reported that regular breakfast consumption, but not morning fasting, slightly increased insulin‐stimulated glucose uptake in primary adipocytes obtained from the lean individuals (Betts et al. 2014). Taken together, the present study suggests that the mechanism responsible for the observed differences could involve alterations in the regulators of GLUT4 translocation, such as more distal insulin signalling components (e.g. AS160) or mediators of the actin and the microtubule cytoskeletal networks (e.g. Rab GTPase activating protein). Additional unbiased global transcriptomic and phospho‐proteomic analyses may wish to fully address the complex molecular mechanisms responsible for morning fasting‐induced alterations in adipose tissue biology and whole‐body metabolism.

The present work by Gonzalez et al. (2018) provides novel and important insights into understanding adaptive responses of adipose tissue to prolonged morning fasting compared to regular breakfast consumption. Nonetheless, many interesting questions regarding the effects of morning fasting on adipose tissue biology still remain. For example, does prolonged morning fasting induced by skipping breakfast affect adipose tissue circadian clocks? Emerging evidence has revealed the fascinating molecular and physiological interplay between nutrition, metabolism and circadian rhythm. Indeed, it was recently reported that clock genes, master regulators of circadian rhythm, play a pivotal role in regulating the adaptive lipolytic response of adipose tissue to fasting and thus whole‐body NEFA metabolism (Shostak et al. 2013). Early nocturnal meal skipping, which mimics the effect of prolonged morning fasting in people, significantly alters clock genes and NEFA metabolism‐related genes in adipose tissue of normal mice (Yoshida et al. 2012). Consistent with these findings from rodent studies, meal timing affects the diurnal variations in expression of adipose tissue clock genes and glucose metabolism in healthy people under constant routine conditions (Wehrens et al. 2017). In addition, recent data obtained from lipidomics analysis of human skeletal muscle suggest that circadian clock genes are involved in regulating diurnal oscillations of numerous lipid metabolites and their biosynthetic enzymes in vivo (Loizides‐Mangold et al. 2017). It will therefore be of great interest to evaluate the effects of prolonged morning fasting on the diurnal expression patterns of adipose tissue clock genes and cellular and whole‐body NEFA metabolism in future studies that involve the integrative multi‐omics analysis of blood and adipose tissue biopsy samples serially collected over 24 h under constant conditions.

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Competing interests

None declared.