Biology subjects

Pulpitel, T.

Publications and source records attributed to Pulpitel, T..

3 recordsLinked to original sources

bioRxiv2025

Dietary macronutrients modulate the proteome of brown adipose tissue in males and their female offspring

Brown adipose tissue (BAT) dissipates energy as heat, not only under cold exposure but also in the dissipation of excess ingested energy. Therefore, enhancing BAT activity is a potential avenue to combat weight gain. Dietary macronutrient composition influences BAT size and has recently been shown to influence BAT size of daughters through the patriline of C57BL/6J mice. However, the effects of macronutrient composition and any paternal effects on BAT function have yet to be characterised. Using the Geometric Framework for Nutrition, we investigated the effects of macronutrient composition on the BAT proteome in male mice and intergenerational effects in their offspring. In fathers, >50% of the proteome was affected by macronutrient composition, with distinct clusters of proteins that responded in similar ways. We identified two clusters with inverse patterns that correlated with BAT mass. Notably, UCP1 was reduced on low fat diets that promoted increased BAT mass, while there were increased levels of proteins involved in protein turnover on those same diets. The same diets also led to a reduction in proteins involved in purine biosynthesis (often UCP1 inhibitors). We did not find any effects of paternal diet on the BAT proteome in sons, but paternal protein intake negatively affected basigin expression in daughters - a protein that regulates UCP1 transcription. Our results highlight that dietary macronutrient composition in males remodels the protein expression landscape of BAT, and pre-conceptionally reprograms BAT expression profiles of female offspring.

molecular biology↗

bioRxiv2023

Hepatic Lipid Droplet-Associated Proteome Changes Distinguish Dietary-Induced Fatty Liver from Insulin Resistance in Male Mice.

Fatty liver is characterised by the expansion of lipid droplets and is associated with the development of many metabolic diseases, including insulin resistance, dyslipidaemia and cardiovascular disease. We assessed the morphology of hepatic lipid droplets and performed quantitative proteomics in lean, glucose-tolerant mice compared to high-fat diet (HFD) fed mice that displayed hepatic steatosis and glucose intolerance as well as high-starch diet (HStD) fed mice who exhibited similar levels of hepatic steatosis but remained glucose tolerant. Both HFD and HStD-fed mice had more and larger lipid droplets than Chow-fed animals. We observed striking differences in liver lipid droplet proteomes of HFD and HStD-fed mice compared to Chow-fed mice, with fewer differences between HFD and HStD. Taking advantage of our diet strategy, we identified a fatty liver lipid droplet proteome consisting of proteins common in HFD- and HStD-fed mice. Likewise, a proteome associated with glucose tolerance that included proteins common in Chow and HStD but not HFD-fed mice was identified. Notably, glucose intolerance was associated with changes in the ratio of adipose triglyceride lipase (ATGL) to perilipin 5 (PLIN5) in the lipid droplet proteome, suggesting dysregulation of neutral lipid homeostasis in glucose-intolerant fatty liver, which supports bioactive lipid synthesis and impairs hepatic insulin action. We conclude that our novel dietary approach uncouples ectopic lipid burden from insulin resistance-associated changes in the hepatic lipid droplet proteome.

cell biology↗

bioRxiv2022

Insulin sensitivity is preserved in mice made obese by feeding a high starch diet

Obesity is generally associated with insulin resistance in liver and muscle and increased risk of developing type 2 diabetes, however there is a population of obese people that remain insulin sensitive. Similarly, recent work suggests that mice fed high carbohydrate diets can become obese without apparent glucose intolerance. To investigate this phenomenon further, we fed mice either a high fat (Hi-F) or high starch (Hi-ST) diet and measured adiposity, glucose tolerance, insulin sensitivity and tissue lipids compared to control mice fed a standard laboratory chow. Both Hi-ST and Hi-F mice accumulated a similar amount of fat and tissue triglyceride compared to chow-fed mice. However while Hi-F diet mice developed glucose intolerance as well as liver and muscle insulin resistance (assessed via euglycemic/hyperinsulinemic clamp), obese Hi-ST mice maintained glucose tolerance and insulin action similar to lean, chow-fed controls. This preservation of insulin action despite obesity in Hi-ST mice was associated with differences in de novo lipogenesis and levels of C22:0 ceramide in liver and C18:0 ceramide in muscle. This indicates that dietary manipulation can influence insulin action independently of the level of adiposity and that the presence of specific ceramide species correlate with these differences.

physiology↗