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Diabetes, Overweight, and Obesity
Published in Michelle Tollefson, Nancy Eriksen, Neha Pathak, Improving Women's Health Across the Lifespan, 2021
In healthy, normoglycemic women, estrogen-mediated gluteal-femoral adipose storage provides a safer lipid reservoir for energy distribution, there is less myocardial and pericardial fat,44 and increased active brown adipose tissue leading to lower cardiometabolic risk.45 Central obesity is associated with diabetes and metabolic syndrome,38,46 and elevated BMI and accumulation of intramyocellular lipids correlate with insulin resistance, obesity, and T2DM in women. 47,48 Women may be more resistant than men to losing fat stores, but will oxidize more fat than glucose during endurance exercise training.49,50
Insulin Resistance and Glucose Regulation
Published in Awanish Kumar, Ashwini Kumar, Diabetes, 2020
Insulin receptor substrate (IRS-1 and IRS-2) proteins are the major proteins directly attached to the IR and convey the signalling cascade further. In a simple explanation of insulin action, insulin binds to the IR present on the cell membrane. The IR gets autophosphorylated at tyrosine residues and further activates IRS-1 and IRS-2. These proteins further activate PI-3 kinase and finally Akt/PKB. Akt finally activates and recruits GLUT-4 (the primary insulin responsive glucose transporter) on the cell membrane so that it can bring the circulating glucose inside the cell. Free fatty acids are seen to become stored in non-adipose cells, leading to increased intramyocellular lipid depots, and leading to insulin resistance. It has also been shown that FFA-induced insulin resistance is related to downregulation of the insulin receptor (IR) gene. FFA also inhibits the activation of PI-3 kinase in the skeletal muscle cells. It has also been found that saturated fats block the insulin activation of Akt/PKB signalling. These FFA inhibitory actions finally result in diminished GLUT-4 translocation to membranes, finally increasing the plasma glucose [16]. FFAs also serve as a great substrate for hepatic TG synthesis and hepatic gluconeogenesis which results in elevated plasma VLDL and hyperglycaemia.
Type 2 Diabetes in Childhood
Published in Emmanuel C. Opara, Sam Dagogo-Jack, Nutrition and Diabetes, 2019
The elevations in plasma FFAs, TG, and circulating adipocytokines in the setting of leptin resistance have profound effects on insulin action in skeletal muscle. Analysis of muscle biopsies from insulin-resistant adults shows reductions in tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS)-1, decreased IRS-1–associated PI-3 kinase activity, and impaired threonine- and serine-phosphorylation of Akt. The defects in insulin signaling are thought to be induced by intramyocellular accumulation of TG (IMCL) or other lipid species. High intramyocellular lipid content (IMCL) in skeletal muscle has been associated with IGT in obese youth. Nondiabetic, nonobese adult patients with high IMCL have also been shown to have greater IR in skeletal muscle than adults with normal IMCL [6]. The myocellular lipid accumulation may reflect in part an inherited defect in mitochondrial oxidative phosphorylation [7]. Inhibition of Akt phosphorylation impairs skeletal muscle glucose uptake by reducing glucose transporter 4 (GLUT-4) expression, translocation, and/or activity [8,9]. The result is a progressive decrease in insulin-stimulated nonoxidative glucose disposal.
Impact of methionine restriction on muscle aerobic metabolism and hypertrophy in young and old mice on an obesogenic diet
Published in Growth Factors, 2022
Anandini Swaminathan, Leonardo Cesanelli, Tomas Venckunas, Hans Degens
In line with earlier work (Messa et al. 2020), we observed that young mice fed a HFD have a higher SDH activity than those on a control diet. It has been shown that a HFD may increase the SDH activity in muscle fibres from young, but not old mice (Messa et al. 2020). As we discussed previously, such a diminished responsiveness of the oxidative metabolism to a HFD in muscles from old mice may result in a lesser ability to oxidise fatty acids and consequently a more rapid intramyocellular lipid accumulation in old than young muscles (Degens, Swaminathan, and Tallis 2021). Here we extend this observation that also an overload-induced increase in SDH activity seen in young mice did not occur in old mice except—but to a much lesser extent than in young animals—if they were fed MR + HFD. It thus appears that MR has only a limited impact on mitochondrial biogenesis in muscle, in contrast to the stimulation of mitochondrial biogenesis in brain (Naudí et al. 2007). We have no explanation for this discrepancy, but it may reflect that the effects of MR on oxidative metabolism are tissue specific.
Vitamin D inadequacy combined with high BMI affects paraspinal muscle atrophy and pain intensity in postmenopausal women
Published in Climacteric, 2022
H. Chen, H.-W. Xu, S.-B. Zhang, Y.-Y. Yi, S.-J. Wang
Many studies have recently shown that vitamin D deficiency can cause skeletal muscle atrophy [12]. Age-related muscle degeneration is a relatively complex process involving muscle degeneration and FI; moreover, the musculoskeletal system in elderly people is more susceptible to vitamin D deficiency because the expression of vitamin D receptors in muscles decreases with age [21]. FI is another important factor leading to muscle degeneration; FI inside and outside muscle cells affects the function of the muscular system. Redzic et al. [22] studied 20 community-dwelling adults aged 65–85 years and found that the vitamin D status is related to intramyocellular lipids in older adults independent of body mass and physical activity. In addition, the serum vitamin D and vitamin D receptor levels decrease with age; this is accompanied by increased physiological muscle degeneration, with vitamin D deficiency and aging leading to FI of muscle and activation of proteolytic pathways. Moreover, the present study showed that women in the high BMI with vitamin D deficiency/insufficiency group had lower physical activity levels, lower HGS and higher FI of PSMs than the other groups. Poor muscle strength is closely associated with low physical activity [23], and different activity levels may have different impacts on muscle strength and function. Indeed, the effectiveness of physical activity on increased muscle strength and physical performance has been proven [24,25].
The impact of body composition on treatment in ovarian cancer: a current insight
Published in Expert Review of Clinical Pharmacology, 2021
Veronica McSharry, Kate Glennon, Amy Mullee, Donal Brennan
Intramyocellular lipid decreases upon acute exercise and almost completely disappears after marathon running [67]. Low SMD is also associated with weight loss in cancer patients [67]. Early identification of low SMD may permit the use of specialized multimodal interventions prior to, and after surgery, including nutritional support, exercise intervention and psychological support. It is hypothesized that low SMD is associated with reduced survival for a variety of reasons. Skeletal muscle are known to secrete cytokines and other peptides which may encourage growth of tumor cells [80,81]. Reduced skeletal muscle density can therefore lead to an altered myokine response and defective regulation of tumor cells. Furthermore, low SMD is also associated hyperinsulinemia and insulin resistance [69]. Hyperinsulinemia can promote tumor cell proliferation and a decline in the synthesis of insulin-like growth factor-1 (IGF-1) binding protein [82]. The activation of IGF-1 may also lead to tumor cell growth [82]. Low SMD may also impact on OS by promoting increased systemic inflammation [83].