Lipid Science & Technology

Metabolic syndrome is a complex disease that encompasses obesity, type 2 diabetes, hypertension and hyperlipidemia. Poor

dietary habits and sedentary life style lead to impaired adipose tissue fuel handling and ectopic lipid deposition in vital

organs such a liver, pancreas, muscle and heart. Transcriptional coactivators peroxisome proliferator receptor coactivator 1 alpha

and beta (PGC1α, PGC1β) as well as sterol regulatory element-binding proteins (SREBPs) play vital roles in regulating the lipid

oxidizing and lipogenic genes and thereby control the progression of obesity and metabolic syndrome. AMP-activated protein

kinase (AMPK) and Sirtuins (SIRT) are two metabolic fuel sensors that directly affect PGCs and SEREBPs through phosphorylation

and deacetylation, respectively. A number of natural modulators have a direct impact on the intracellular status of AMPK and

SIRTs, and thereby may play vital roles in maintaining lipid homeostasis. We show that low omega3-polyunsaturated fatty acids

(low-ω3FA) and soy proteins effectively attenuate high-fat diet-induced hyperlipidemia and hepatosteatosis. They also prevent the

downregulation of hepatic SIRT1 and PGC1α and their target fatty acid oxidation pathway genes and attenuate the upregulation

of hepatic PGC1α and SREBP1c and their target lipogenic pathway genes via the phosphorylation of AMPK. Similarly, dietary

curcumin protects against high-ω3FA-induced hepatosteatosis. Simultaneously, polyphenol, quercetin upregulates paraoxonase 1

(PON1) mRNA and causes significant increase in serum PON1 and homocysteine thiolactonase (HCT), the key anti-atherogenic

enzymes. Moreover, quercetin protects against high-ω3FA-induced oxidative stress by increasing the antioxidant glutathione

and decreasing the toxic lipid peroxidation product 4-hydroxynonenal. He will discuss the status of the relative roles of these

transcriptional coactivators, and the central roles of AMPK and SIRT in the maintenance of lipid homeostasis with special

emphasis on how novel dietary supplements such as low-ω3FA, soy proteins, and curcumin may serve adjunct therapeutic agents

in the treatment of obesity, metabolic syndrome and cardiovascular risks in conjunction with traditional drug therapy.

Recent Publications

1. Canto C and Auwerx J (2009) PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure.

Current Opinion in Lipidology 20(2):98-105.

2. Reyes Gordillo K, Shah R, Varatharajalu R, Garige M, Leckey L C and Lakshman M R (2016) Low-ω3 fatty acid and soy protein

attenuate alcohol-induced fatty liver and injury by regulating the opposing lipid oxidation and lipogenic signaling pathways.

Oxidative Medicine and Cellular Longevity doi: 10.1155/2016/1840513.

3. Passi M, Garige M, Gong M, Leckey L, Nylen E, Shah R, Lakshman MR. Protective roles of polyphenols against the pathogenesis

of diabetes, cardiovascular and other chronic diseases. Curr Top Biochem Res. 15: 109-126, 2014.

4. Varatharajalu R, Garige M, Leckey LC, Arellanes-Robledo J, Reyes-Gordillo K, Shah R and Lakshman M R (2014) Adverse

signaling of scavenger receptor class B1 and PGC1s in alcoholic hepatosteatosis and steatohepatitis, and protection by betaine in

rat. American Journal of Pathology 184(7):2035-44.