Macey, M (2020) Fibre and sex specific differences in mitochondrial content and subcellular distribution and morphology or lipid droplets in skeletal muscle biopsies obtained from lean, obese and type 2 diabetes patients. Masters thesis, Liverpool John Moores University.

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Abstract

Intramuscular triglycerides (IMTG) are stored in lipid droplets (LD) in skeletal muscle, and it is thought that subcellular location, size and number of LDs relate to insulin sensitivity (IS) more so than IMTG content alone. Reduced expression and function of mitochondria has been implicated in the development of insulin resistance, leading to an accumulation of IMTG due to reduced oxidative capacity. The aim of the present study was to 1) establish a better understanding of the sex differences in the relationship between LD profile, mitochondrial density and the development of insulin resistance thereby 2) contributing to current and future research improving insulin sensitivity and preventing the progression of insulin resistance. The study investigated the hypothesis that 1) females have greater LD stores compared to males whilst maintaining insulin sensitivity, and 2) that type two diabetes (T2D) patients have greater LD stores compared to their lean and obese counterparts. Muscle biopsies were obtained from 48 male (n=24) and female (n=24) participants, categorised into groups (n=16/group) based on metabolic health; lean, obese and T2D. Cryosections (5μm) were stained using appropriate antibodies targeting myosin heavy chain I (MHC I) and MHC IIa. LDs were stained using bodipy 493/503 and mitochondria using mouse monoclonal anti-OxPhos complex IV (COXIV). Images were obtained using widefield and confocal fluorescence microscopy. In males, LD content was two-fold greater (P<0.05) within both the central and peripheral (5μm below cell membrane) regions of the type I and II fibres due to a two-fold increase in LD density (P<0.05) alongside larger LDs by one-fold (P<0.05) in comparison to females; thereby contradicting the first hypothesis. However, in agreement with the second hypothesis LD content was two-fold greater (P<0.05) in male T2D specifically within the central region of the type IIa fibres compared to the lean and obese males; primarily driven through larger LDs by one-fold (P<0.05). Furthermore, mitochondrial density followed a hierarchical distribution (TI>TII; P<0.001) in both males and females, with no differences observed between sexes or metabolic health status (P>0.05). In conclusion, this thesis presents novel data on sex differences in LD profile, mitochondrial density and insulin resistance and suggests a potential sex paradox; whereby reduced sex hormone production in post-menopausal females, alongside inactivity maybe more important determinants of insulin sensitivity than LD profile alone.

Item Type:	Thesis (Masters)
Uncontrolled Keywords:	Endocrinology; Lipid droplets; Mitochondria; Obesity; Type 2 diabetes; Skeletal muscle; Metabolism
Subjects:	R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport & Exercise Sciences
Date Deposited:	25 Sep 2020 11:16
Last Modified:	08 Nov 2022 13:44
DOI or ID number:	10.24377/LJMU.t.00013702
Supervisors:	Strauss, J, Shepherd, S and Wagenmakers, A
URI:	https://researchonline.ljmu.ac.uk/id/eprint/13702

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