• Dietary alpha-lactalbumin alters energy balance, gut microbiota composition and intestinal nutrient transporter expression in high-fat diet fed mice

      Boscaini, Serena; Cabrera-Rubio, Raul; Speakman, John R.; Cotter, Paul D.; Cryan, John F.; Nilaweera, Kanishka; Teagasc Walsh Fellowship Programme; Science Foundation Ireland; BBSRC; Teagasc; et al. (Cambridge University Press, 2019-03-05)
      Recently there has been a considerable rise in the frequency of metabolic diseases, such as obesity, due to changes in lifestyle and resultant imbalances between energy intake and expenditure. Whey proteins are considered as potentially important components of a dietary solution to the obesity problem. However, the roles of individual whey proteins in energy balance remain poorly understood. This study investigated the effects of a high fat diet (HFD) containing alphalactalbumin (LAB), a specific whey protein, or the non-whey protein casein (CAS), on energy balance, nutrient transporters expression, and enteric microbial populations. C57BL/6J mice (n = 8) were given a HFD containing either 20% CAS or LAB as protein sources or a low-fat diet (LFD) containing CAS for 10 weeks. HFD-LAB fed mice showed a significant increase in cumulative energy intake (P=0.043), without differences in body weight, energy expenditure, locomotor activity, respiratory exchange ratio or subcutaneous and epididymal adipose tissue weight. HFD-LAB intake led to a decrease in the expression of glucose transporter glut2 in the ileum (P=0.05)and in the fatty acid transporter cd36 (P<0.001) in both ileum and jejunum. This suggests a reduction of absorption efficiency within the small intestine in the HFD-LAB group. DNA from faecal samples was used for 16S rRNA-based assessment of intestinal microbiota populations; the genera Lactobacillus, Parabacteroides and Bifidobacterium were present in significantly higher proportions in the HFD-LAB group. These data indicate a possible functional relationship between gut microbiota, intestinal nutrient transporters and energy balance, with no impact on weight gain.
    • Protein quality and quantity influence the effect of dietary fat on weight gain and tissue partitioning via host-microbiota changes

      Nychyk, Oleksandr; Barton, Wiley; Rudolf, Agata M.; Boscaini, Serena; Walsh, Aaron; Bastiaanssen, Thomaz F.S.; Giblin, Linda; Cormican, Paul; Chen, Liang; Piotrowicz, Yolanda; et al. (Elsevier BV, 2021-05-11)
      We investigated how protein quantity (10%–30%) and quality (casein and whey) interact with dietary fat (20%–55%) to affect metabolic health in adult mice. Although dietary fat was the main driver of body weight gain and individual tissue weight, high (30%) casein intake accentuated and high whey intake reduced the negative metabolic aspects of high fat. Jejunum and liver transcriptomics revealed increased intestinal permeability, low-grade inflammation, altered lipid metabolism, and liver dysfunction in casein-fed but not whey-fed animals. These differential effects were accompanied by altered gut size and microbial functions related to amino acid degradation and lipid metabolism. Fecal microbiota transfer confirmed that the casein microbiota increases and the whey microbiota impedes weight gain. These data show that the effects of dietary fat on weight gain and tissue partitioning are further influenced by the quantity and quality of the associated protein, primarily via effects on the microbiota.
    • Regulation of intestinal growth in response to variations in energy supply and demand

      Nilaweera, Kanishka; Speakman, John R.; Science Foundation Ireland; Biotechnology and Biological Sciences Research Council (BBSRC); SFI/16/BBSRC/3389; BB/P009875/1 (Wiley, 2018-12-03)
      The 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.
    • Whey protein effects on energy balance link the intestinal mechanisms of energy absorption with adiposity and hypothalamic neuropeptide gene expression

      Nilaweera, Kanishka; Cabrera-Rubio, Raul; Speakman, John R.; O'Connor, Paula M.; McAuliffe, Ann Marie; Guinane, Caitriona M.; Lawton, Elaine M.; Crispie, Fiona; Aguillera, Monica; Stanley, Maurice; et al. (American Physiological Society, 21/03/2017)
      We tested the hypothesis that dietary whey protein isolate (WPI) affects the intestinal mechanisms related to energy absorption and that the resulting energy deficit is compensated by changes in energy balance to support growth. C57BL/6 mice were provided a diet enriched with WPI with varied sucrose content, and the impact on energy balance-related parameters was investigated. As part of a high-sucrose diet, WPI reduced the hypothalamic expression of pro-opiomelanocortin gene expression and increased energy intake. The energy expenditure was unaffected, but epididymal weight was reduced, indicating an energy loss. Notably, there was a reduction in the ileum gene expression for amino acid transporter SLC6a19, glucose transporter 2, and fatty acid transporter 4. The composition of the gut microbiota also changed, where Firmicutes were reduced. The above changes indicated reduced energy absorption through the intestine. We propose that this mobilized energy in the adipose tissue and caused hypothalamic changes that increased energy intake, acting to counteract the energy deficit arising in the intestine. Lowering the sucrose content in the WPI diet increased energy expenditure. This further reduced epididymal weight and plasma leptin, whereupon hypothalamic ghrelin gene expression and the intestinal weight were both increased. These data suggest that when the intestine-adipose-hypothalamic pathway is subjected to an additional energy loss (now in the adipose tissue), compensatory changes attempt to assimilate more energy. Notably, WPI and sucrose content interact to enable the component mechanisms of this pathway.
    • Whey protein effects on energy balance link the intestinal mechanisms of energy absorption with adiposity and hypothalamic neuropeptide gene expression

      Nilaweera, Kanishka; Cabrera-Rubio, Raul; Speakman, John R.; O'Connor, Paula M.; McAuliffe, Ann Marie; Guinane, Caitriona M.; Lawton, Elaine M.; Crispie, Fiona; Aguillera, Monica; Stanley, Maurice; et al. (American Physiological Society, 19/06/2017)
      We tested the hypothesis that dietary whey protein isolate (WPI) affects the intestinal mechanisms related to energy absorption and that the resulting energy deficit is compensated by changes in energy balance to support growth. C57BL/6 mice were provided a diet enriched with WPI with varied sucrose content, and the impact on energy balance-related parameters was investigated. As part of a high-sucrose diet, WPI reduced the hypothalamic expression of pro-opiomelanocortin gene expression and increased energy intake. The energy expenditure was unaffected, but epididymal weight was reduced, indicating an energy loss. Notably, there was a reduction in the ileum gene expression for amino acid transporter SLC6a19, glucose transporter 2, and fatty acid transporter 4. The composition of the gut microbiota also changed, where Firmicutes were reduced. The above changes indicated reduced energy absorption through the intestine. We propose that this mobilized energy in the adipose tissue and caused hypothalamic changes that increased energy intake, acting to counteract the energy deficit arising in the intestine. Lowering the sucrose content in the WPI diet increased energy expenditure. This further reduced epididymal weight and plasma leptin, whereupon hypothalamic ghrelin gene expression and the intestinal weight were both increased. These data suggest that when the intestine-adipose-hypothalamic pathway is subjected to an additional energy loss (now in the adipose tissue), compensatory changes attempt to assimilate more energy. Notably, WPI and sucrose content interact to enable the component mechanisms of this pathway.
    • Whey protein isolate decreases murine stomach weight and intestinal length and alters the expression of Wnt signalling-associated genes

      McAllan, Liam; Speakman, John R.; Cryan, John F.; Nilaweera, Kanishka (Cambridge University Press, 13/01/2015)
      The present study examined the underlying mechanisms by which whey protein isolate (WPI) affects energy balance. C57BL/6J mice were fed a diet containing 10 % energy from fat, 70 % energy from carbohydrate (35 % energy from sucrose) and 20 % energy from casein or WPI for 15 weeks. Mice fed with WPI had reduced weight gain, cumulative energy intake and dark-phase VO2 compared with casein-fed mice (P< 0·05); however, WPI intake had no significant effects on body composition, meal size/number, water intake or RER. Plasma levels of insulin, TAG, leptin, glucose and glucagon-like peptide 1 remained unchanged. Notably, the intake of WPI reduced stomach weight and both length and weight of the small intestine (P< 0·05). WPI intake reduced the gastric expression of Wingless/int-1 5a (Wnt5a) (P< 0·01) and frizzled 4 (Fzd4) (P< 0·01), with no change in the expression of receptor tyrosine kinase-like orphan receptor 2 (Ror2) and LDL receptor-related protein 5 (Lrp5). In the ileum, WPI increased the mRNA expression of Wnt5a (P< 0·01) and caused a trend towards an increase in the expression of Fzd4 (P= 0·094), with no change in the expression of Ror2 and Lrp5. These genes were unresponsive in the duodenum. Among the nutrient-responsive genes, WPI specifically reduced ileal mRNA expression of peptide YY (P< 0·01) and fatty acid transporter protein 4 (P< 0·05), and decreased duodenal mRNA expression of the insulin receptor (P= 0·05), with a trend towards a decreased expression of Na–glucose co-transporter 1 (P= 0·07). The effects of WPI on gastrointestinal Wnt signalling may explain how this protein affects gastrointestinal structure and function and, in turn, energy intake and balance.