89
mainly by elevation in AKT phosphorylation and reduction in PTEN activation in
liver [42]. Whereas, an abnormality in mitochondrial function that leads towards
incomplete fatty acid oxidation is also a potential contributor in insulin resistance
and associated T2DM [43]. Truly, this abnormality in mitochondrial function also
provokes intracellular accumulation of diacylglycerol (DAG), an active lipid associated with downregulation of insulin signaling pathway and so, accordingly potentiates insulin resistance [44]. Several studies have also elucidated that abnormal
elevation of DAG is associated with Protein Kinase C activation, which subsequently disturbs the normal insulin stimulated signaling, and ultimately giving rise
to insulin resistance and afterward T2DM [45]. Correspondingly, augmenting
sphingolipids in non-adipose tissues is potential mediator of insulin resistance and
also establishes strong association with cardiac failure, diabetes, hypertension, and
atherosclerosis [46].
Evidently, the therapeutic approach to prevent and obviating this metabolic disorder is diet mainly composed of vegetables and fruits along with minimum use of
saturated fat. Dietary Guidelines for Americans recommended that adaptation to
dietary guidelines lowers the circulating ceramide level, which ultimately ends up
in improving insulin sensitivity [47]. So, disturbance in lipid metabolism has contribution in incidence and progression of insulin resistance and T2DM.
Polycystic Ovary Syndrome
PCOS is a complicated metabolic syndrome, primarily associated with hyperandrogenism as well as chronic anovulation, with the prevalence of 6–10% in women
of reproductive age [48]. Generally linked with multiple pathophysiology such as
endocrine, genetics, environmental, and metabolic factors. Women victimized by
PCOS have to face many complications along with many metabolic derangements
like hypertension, obesity, dyslipidemia, and insulin resistance. Such women are
also more vulnerable to early onset of cardiovascular complications [49].
Accordingly, women with PCOS possess higher abdominal adiposity as compared
to normal women having comparable BMI. Likewise, this phenotypic expression
of adiposity may start in adolescence. Furthermore, elevated subcutaneous adiposity may start in adolescence. Additionally, elevated subcutaneous abdominal adiposity in PCOS women dictates diminished ability of adipose tissues for safely
storing fat [50].
The chief manifestation of PCOS is diluted ovulation, particularly interlinked
with obesity or other lipid metabolic disorders. The prevalence of obese women
with PCOS is nearly 50–80%. Actually, obesity has association with irregular adipokine secretion, combined with increased free fatty acids that finally end up in
insulin resistance. Generally, 20% of obese women having PCOS demonstrated
abnormal glucose tolerance [51]. Despite the exact pathogenesis of PCOS is unclear,
a number of mechanisms has been proposed and still debatable. Insulin resistance
and subsequent hyperinsulinemia and atherogenic dyslipidemia are central to the
5 Impaired Lipid Metabolism in Metabolic Disorders
mainly by elevation in AKT phosphorylation and reduction in PTEN activation in
liver [42]. Whereas, an abnormality in mitochondrial function that leads towards
incomplete fatty acid oxidation is also a potential contributor in insulin resistance
and associated T2DM [43]. Truly, this abnormality in mitochondrial function also
provokes intracellular accumulation of diacylglycerol (DAG), an active lipid associated with downregulation of insulin signaling pathway and so, accordingly potentiates insulin resistance [44]. Several studies have also elucidated that abnormal
elevation of DAG is associated with Protein Kinase C activation, which subsequently disturbs the normal insulin stimulated signaling, and ultimately giving rise
to insulin resistance and afterward T2DM [45]. Correspondingly, augmenting
sphingolipids in non-adipose tissues is potential mediator of insulin resistance and
also establishes strong association with cardiac failure, diabetes, hypertension, and
atherosclerosis [46].
Evidently, the therapeutic approach to prevent and obviating this metabolic disorder is diet mainly composed of vegetables and fruits along with minimum use of
saturated fat. Dietary Guidelines for Americans recommended that adaptation to
dietary guidelines lowers the circulating ceramide level, which ultimately ends up
in improving insulin sensitivity [47]. So, disturbance in lipid metabolism has contribution in incidence and progression of insulin resistance and T2DM.
Polycystic Ovary Syndrome
PCOS is a complicated metabolic syndrome, primarily associated with hyperandrogenism as well as chronic anovulation, with the prevalence of 6–10% in women
of reproductive age [48]. Generally linked with multiple pathophysiology such as
endocrine, genetics, environmental, and metabolic factors. Women victimized by
PCOS have to face many complications along with many metabolic derangements
like hypertension, obesity, dyslipidemia, and insulin resistance. Such women are
also more vulnerable to early onset of cardiovascular complications [49].
Accordingly, women with PCOS possess higher abdominal adiposity as compared
to normal women having comparable BMI. Likewise, this phenotypic expression
of adiposity may start in adolescence. Furthermore, elevated subcutaneous adiposity may start in adolescence. Additionally, elevated subcutaneous abdominal adiposity in PCOS women dictates diminished ability of adipose tissues for safely
storing fat [50].
The chief manifestation of PCOS is diluted ovulation, particularly interlinked
with obesity or other lipid metabolic disorders. The prevalence of obese women
with PCOS is nearly 50–80%. Actually, obesity has association with irregular adipokine secretion, combined with increased free fatty acids that finally end up in
insulin resistance. Generally, 20% of obese women having PCOS demonstrated
abnormal glucose tolerance [51]. Despite the exact pathogenesis of PCOS is unclear,
a number of mechanisms has been proposed and still debatable. Insulin resistance
and subsequent hyperinsulinemia and atherogenic dyslipidemia are central to the
5 Impaired Lipid Metabolism in Metabolic Disorders