Eat And Death: Chronic Over-Eating - PubMed

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Abstract

Obesity-related co-morbidities decrease life quality, reduce working ability and lead to early death. The total amount of dietary fat consumption may be the most potent food-related risk factor for weight gain. In this respect, dietary intake of high-caloric, high-fat diets due to chronic over-eating and sedentary lifestyle lead to increased storage of triglycerides not only in adipose tissue but also ectopically in other tissues . Increased plasma concentrations of non-esterified free fatty acids and lipid-overloaded hypertrophic adipocytes may cause insulin resistance in an inflammation-independent manner. Even in the absence of metabolic disorders, mismatch between fatty acid uptake and utilization leads to the accumulation of toxic lipid species resulting in organ dysfunction. Lipid-induced apoptosis, ceramide accumulation, reactive oxygen species overproduction, endoplasmic reticulum stress, and mitochondrial dysfunction may play role in the pathogenesis of lipotoxicity. The hypothalamus senses availability of circulating levels of glucose, lipids and amino acids, thereby modifies feeding according to the levels of those molecules. However, the hypothalamus is also similarly vulnerable to lipotoxicity as the other ectopic lipid accumulated tissues. Chronic overnutrition most likely provides repetitive and persistent signals that up-regulate inhibitor of nuclear factor kappa B kinase beta subunit/nuclear factor kappa B (IKKβ/NF-κB) in the hypothalamus before the onset of obesity. However, the mechanisms by which high-fat diet induced peripheral signals affect the hypothalamic arcuate nucleus remain largely unknown. In this chapter, besides lipids and leptin, the role of glucose and insulin on specialized fuel-sensing neurons of hypothalamic neuronal circuits has been debated.

Keywords: Adenosine monophosphate‑activated protein kinase (AMPK) activity; Ceramide; Chronic overnutrition; Free fatty acid; Heart failure; Lipotoxicity; Mammalian target of rapamycin (mTOR); Mitochondria; Obesity; Obesity paradox; Overfeeding; Uncoupling protein (UCP).

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