Lipoexpediency: de novo lipogenesis as a metabolic signal transmitter

Abstract

De novo lipogenesis, the production of fats from simple precursors, is often dismissed as irrelevant to the pathobiology of obesity caused by positive energy balance due to typical high fat diets. However, emerging data implicate de novo lipogenesis in the generation of metabolic signals that alter disease risk. Exploiting this signaling pathway represents lipoexpediency. Lipoexpediency is the concept of directing fats toward benefit even in the setting of lipid overload, and represents a strategy to complement efforts aimed at improving energy balance. Optimizing lipid signals initiated by key lipogenic enzymes such as fatty acid synthase might limit morbidity in people unlikely to abandon the lifestyle of the sedentary gourmand. The reality of lipid excess An epidemic with limited novel treatment approachesOver 40% of Americans have diabetes or prediabetes [1] and as many as a quarter of American adults have the metabolic syndrome, which predisposes to diabetes and cardiovascular disease [2]. Tobacco use increases health risks that have been decreased by public health measures targeted at smoking, but the adverse effects of obesity will probably negate the beneficial effects of declining tobacco use in the United States by 2020 [3]. The metabolic mayhem promoted by a Western lifestyle has been exported worldwide, and diabetes is now a major and accelerating public health problem in China [4]. Diabetes, obesity, and the metabolic syndrome also increase the risk of nonalcoholic fatty liver disease [5]. Lifestyle changes are difficult to institute given the pressures of Western culture, and other therapies are limited. For example, insulin therapy lowers hemoglobin A1c but may increase adiposity. Statins and reninangiotensin system (RAS) inhibitors decrease but do not eliminate cardiovascular risk, i.e. individuals with dyslipidemia, hypertension, and diabetes are still at considerable risk for heart attacks even when treated with statins and RAS inhibitors. PPAR agonists have a mixed record that is still evolving, and it is unknown if GLP-1 modulators will decrease complications of diabetes and obesity.

The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans

“…In agreement with this concept, an identified population of obese humans can stay free of insulin resistance and are metabolically healthy despite morbid obesity (12). These findings suggest that not all lipids are detrimental for insulin sensitivity and that specific lipid species, when present in the proper location and time, may trigger signals that modulate adaptation to stress (13,14).…”

Effect of different dietary oil sources on the growth performance, blood characteristics, fatty acid profiles, and expression of lipogenic genes in the liver of broiler chickens

“…(Enser et al 2000;Bell et al 2001;Benatmane et al 2011), but only few data on its effect on poultry liver have been found. As we know, liver is the major site of lipogenesis and de novo fatty acid biosynthesis (Lodhi et al 2011), and liver lipid transfer to other tissues through blood and exerting effect on the lipid content and composition. So further research into the effect of dietary fat source on the fatty acid deposition in poultry liver is needed to understand the mechanisms underlying the deposition of PUFA in poultry tissues (muscles, abdominal fat, and eggs).…”

Hepatic oleate regulates adipose tissue lipogenesis and fatty acid oxidation

“…While it is considered to be quantitatively minimal by some ( 6, 7 ), others have demonstrated that DNL-derived lipids can negatively impact metabolic health and contribute to hepatic steatosis and visceral adiposity in humans ( 8-10 ). Of particular importance in the context of whole-body metabolic homeostasis, recent evidence suggests that de novo synthesized fatty acids and lipids serve important signaling and regulatory roles in cellular and systemic metabolism ( 7,11 ).MUFAs are major components of tissue lipids such as TGs, cholesteryl esters (CEs), and GPs , and high levels of MUFAs are inversely associated with metabolic health. The stearoyl-CoA desaturase (SCD) family of enzymes catalyzes the synthesis of MUFAs by insertion of a cis double bond at the ⌬ 9 position of saturated fatty acids.…”

“…While it is considered to be quantitatively minimal by some ( 6, 7 ), others have demonstrated that DNL-derived lipids can negatively impact metabolic health and contribute to hepatic steatosis and visceral adiposity in humans ( 8-10 ). Of particular importance in the context of whole-body metabolic homeostasis, recent evidence suggests that de novo synthesized fatty acids and lipids serve important signaling and regulatory roles in cellular and systemic metabolism ( 7,11 ).…”