Identification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic Metabolism

Abstract

Dysregulation of lipid metabolism in individual tissues can lead to systemic disruption of insulin action and glucose metabolism. Utilizing a comprehensive lipidomic platform and mice deficient in adipose tissue lipid chaperones aP2 and mal1, we explored how metabolic alterations in adipose tissue are linked to whole-body metabolism through lipid signals. A robust increase in de novo lipogenesis rendered the adipose tissue of these mice resistant to the deleterious systemic effects of dietary lipid exposure. Systemic lipid profiling also led to identification of C16:1n7-palmitoleate as an adipose tissue-derived lipid hormone that strongly stimulates muscle insulin action and suppresses hepatosteatosis. Our data reveal a novel, lipid-mediated endocrine network and demonstrate that adipose tissue uses lipokines such as C16:1n7-palmitoleate to communicate with distant organs and regulate systemic metabolic homeostasis.

Is Palmitoleic Acid a Plausible Nonpharmacological Strategy to Prevent or Control Chronic Metabolic and Inflammatory Disorders?

“…SCD-1 is conserved among mammalian species. [17] It is modulated by dietary components: high levels of palmitoleic acid inhibit SCD-1 expression and activity, [3,6] while saturated fatty acids, sucrose, fructose, and alcohol are www.advancedsciencenews.com www.mnf-journal.com known inducers and activators of this enzyme. [18] SCD-1 activity has been estimated by the ratio of palmitoleic to palmitic acids (16:1n-7/16:0) in plasma.…”

“…[16] Palmitoleic acid has been described as a powerful blocker (of activity and expression) of SCD-1, reducing insulin resistance and NAFLD in mice. [3,6] The inhibitory effect of palmitoleic acid on SCD-1 expression depends on the tissue, being less pronounced in adipose tissue and greater in liver of FABP knockout mice, which presented high levels of palmitoleic acid, lower de novo hepatic lipogenesis, and resistance to deleterious effects of high fat diet. [3] Similar inhibition of SCD-1 was observed in adipose tissue of type-2 diabetic mice treated with palmitoleic acid, in which this monounsaturated fatty acid increased insulin sensitivity and controlled NAFLD progression.…”

“…[3,6] The inhibitory effect of palmitoleic acid on SCD-1 expression depends on the tissue, being less pronounced in adipose tissue and greater in liver of FABP knockout mice, which presented high levels of palmitoleic acid, lower de novo hepatic lipogenesis, and resistance to deleterious effects of high fat diet. [3] Similar inhibition of SCD-1 was observed in adipose tissue of type-2 diabetic mice treated with palmitoleic acid, in which this monounsaturated fatty acid increased insulin sensitivity and controlled NAFLD progression. [6] Thus, in murine models of metabolic disease, the modulation of SCD-1 in adipose tissue promoted by palmitoleic acid may be crucial to the metabolic improvements seen.…”

“…[1,2] Palmitoleic acid has been described as produced and released by adipocytes and acting as a lipokine modulating several metabolic processes in other tissues. [3] For example, several studies observed that palmitoleic acid enhanced whole body glucose disposal in rodents, [3][4][5] attenuated hepatic steatosis in high-fatfed and diabetic mice, [3,6] protected pancreatic β cells from death induced by palmitic acid, [7][8][9] and improved the circulating lipid profile in mice [3] and humans. [10] Furthermore, palmitoleic acid supplementation was seen to reduce liver inflammation in mice with nonalcoholic fatty liver disease (NAFLD), [4,11] and to slow the progression of atherosclerosis in obese mice.…”

Organ-Specific Cancer Metabolism and Its Potential for Therapy

“…One proposed mechanism for the correlation between stearoyl-CoA desaturase expression and HCC aggressiveness might be the systemic link to insulin signaling. Specifically, monounsaturated fatty acids could have an insulin-sensitizing function and thus affect glucose uptake, leading to enhanced capacity for cell proliferation [103]. In addition to desaturation of lipids, also de novo lipid synthesis was increased in liver cancer.…”