Regulation of intestinal growth in response to variations in energy supply and demand

Abstract

SummaryThe growth of the intestine requires energy, which is known to be met by catabolism of ingested nutrients. Paradoxically, during whole body energy deficit including calorie restriction, the intestine grows in size. To understand how and why this happens, we reviewed data from several animal models of energetic challenge. These were bariatric surgery, cold exposure, lactation, dietary whey protein intake and calorie restriction. Notably, these challenges all reduced the adipose tissue mass, altered hypothalamic neuropeptide expression and increased intestinal size. Based on these data, we propose that the loss of energy in the adipose tissue promotes the growth of the intestine via a signalling mechanism involving the hypothalamus. We discuss possible candidates in this pathway including data showing a correlative change in intestinal (ileal) expression of the cyclin D1 gene with adipose tissue mass, adipose derived‐hormone leptin and hypothalamic expression of leptin receptor and the pro‐opiomelanocortin gene. The ability of the intestine to grow in size during depletion of energy stores provides a mechanism to maximize assimilation of ingested energy and in turn sustain critical functions of tissues important for survival.

Cold exposure drives weight gain and adiposity following chronic suppression of brown adipose tissue

“…There is also evidence to suggest that intermittent cold-exposure (from 20°C to 4°C) over a period of days increases weight gain and adiposity and that this is associated with transient, intermittent increases in energy intake [21]. Although other mechanisms such as intestinal growth and increased fatty acid absorption [22] may also play a role the impact of BAT, lipectomy on the response to cold-exposure mirrors our own findings and would suggest a compensatory mechanism for heat production in obesity when adaptive thermogenesis is insufficient. Importantly, an increase of c. 0.5g in BAT and of c. 10g in IWAT cannot account for the c. 41g higher weight gain seen in the cold-exposed animals.…”

“…There is also a plausible mechanism linking the gut to this phenotype which needs to be explored. Cold exposure drives intestinal growth, increased fatty acid absorption and paracellular permeability to nutrients [19, 20]. The efficiency of energy utilisation is also sufficient to maintain core body temperature during acute cold exposure [21].…”

Determination of butyric acid dosage based on clinical and experimental studies – a literature review

“…The mechanism of this phenomenon is complex and still under investigation. One of the explanations is increased metabolism of the white fatty tissue, which induces secretion of a number of mediators (probably including leptin) that stimulate, via hypothalamus, intestine growth and cause increased supply of food (through the sensation of hunger) [23]. Experimental models have also shown that deficits in energy supply ('caloric restriction') lead to intestine growth, both quantitative (increase in organ mass and size) and qualitative (increase in intestinal cell amount) [24].…”

Comparative Meta-Analysis of the Effect of Concentrated, Hydrolyzed, and Isolated Whey Protein Supplementation on Body Composition of Physical Activity Practitioners

“…Natural mechanisms of biological compensation such as increased energy expenditure at rest by thermoregulation increased hunger in fasting and intestinal growth modulation are usually expressed in individuals in transition from sedentary to physically active condition, and also from this to physical rigor required by more exhaustive and frequent training routines [51,52,53,54]. Such mechanisms hinder sudden metabolic changes during transition and adaptation stages, so that the general metabolism always tends to be focused on ensuring the maintenance of the homeostatic energy state before routine change, whether of dietary origin or muscle work [51,55,56].…”