`Study Reveals How Polyphenols Lower Insulin Resistance - Olive Oil Times
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Study Reveals How Polyphenols Lower Insulin Resistance

By Daniel Dawson
Jan. 2, 2024 14:12 UTC

A new study sched­uled for pub­li­ca­tion in 2024 has iden­ti­fied how polyphe­nols found in extra vir­gin olive oil affect the mol­e­c­u­lar and cel­lu­lar mech­a­nisms asso­ci­ated with car­diometa­bolic dis­ease and obe­sity.

While more than a decade of research has demon­strated the abil­ity of polyphe­nols to mit­i­gate the neg­a­tive health impacts asso­ci­ated with chronic inflam­ma­tory dis­eases, researchers still have not iden­ti­fied the bio­log­i­cal mech­a­nism through which these results are obtained.

Polyphenols are able to markedly affect gene expres­sion pro­files in diverse meta­bol­i­cally active tis­sues, and in par­tic­u­lar, polyphe­nols seem to pre­vent some of these dam­ages (from insulin resis­tance).- Enzo Nisoli, obe­sity researcher, University of Milan

Previous research by a team of Italian sci­en­tists iden­ti­fied how sys­temic inflam­ma­tion and mito­chon­dr­ial derange­ment and dys­func­tion are two of the prin­ci­pal mech­a­nisms involved in the patho­phys­i­o­log­i­cal processes link­ing fat accu­mu­la­tion to car­diometa­bolic dis­or­ders, such as obe­sity and dia­betes.

The lead­ing hypothe­ses used to explain the health ben­e­fits of extra vir­gin olive oil on inflam­ma­tory dis­eases gen­er­ally focus on the antiox­i­dant prop­er­ties of polyphe­nols to reverse the impacts of inflam­ma­tion. However, researchers said this has still not been directly demon­strated.

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As a result, the Carapelli Nutritional Institute, a sci­en­tific cen­ter ded­i­cated to the study of olive oil and funded by its par­ent com­pany, Deoleo, con­tacted the Italian research team to study the poten­tial mol­e­c­u­lar and cel­lu­lar mech­a­nisms involved in the ben­e­fi­cial effects of olive oil.

The researchers were also inter­ested in deter­min­ing the role of dif­fer­ent com­po­nents of olive oil – polyphe­nols, lipid deriv­a­tive mol­e­cules, includ­ing squa­lene and toco­pherols, and monoun­sat­u­rated fatty acids – on the asso­ci­ated ben­e­fi­cial effects of extra vir­gin olive oil con­sump­tion on car­diometa­bolic syn­dromes.

Enzo Nisoli, an obe­sity researcher at the University of Milan and co-author of the study, said the team divided the mice into five groups and fed each group a spe­cific diet.

The con­trol group con­sumed a low-fat chow diet, where fat com­prised nine per­cent of total calo­rie con­sump­tion and was com­prised of soy­bean oil, a polyun­sat­u­rated fat.

The other four groups con­sumed diets con­tain­ing 40 per­cent of calo­ries from fat. In each diet, 14 per­cent of fat con­sump­tion com­prised soy­bean oil, a source of linoleic acid, which is essen­tial for mam­mal sur­vival.

The four eat­ing pro­grams included a diet com­prised of lard, a sat­u­rated fat; the EVO Pol+ diet, com­prised of polyphe­nol-enriched extra vir­gin olive oil with squa­lene and toco­pherol; the EVO Pol- diet, com­prised of polyphe­nol-deprived extra vir­gin olive oil with squa­lene and toco­pherol; and a hazel­nut oil diet with only toco­pherol.

Researchers for all groups con­trolled total calo­rie con­sump­tion and lev­els of exer­cise.

“Comparing all these diets, you can obtain infor­ma­tion on the rel­e­vance of a sin­gle com­po­nent of the extra vir­gin olive oil induc­ing even­tual phe­no­typic and mol­e­c­u­lar dif­fer­ences,” Nisoli told Olive Oil Times.

The researchers per­formed a long exper­i­ment with the five diets con­trol­ling glu­cose home­osta­sis at var­i­ous points and, at the end of the exper­i­ment, extracted white and brown adi­pose tis­sue from the liver and skele­tal cells for study.

According to Nisoli, the accu­mu­la­tion of func­tional adi­pose tis­sue in diverse regions of the body ​“is the first stage in pre­dis­posed patients to dif­fer­ent stages of [car­diometa­bolic] syn­drome that can evolve into clin­i­cal car­dio­vas­cu­lar dis­ease or kid­ney dis­ease with alter­ations in the heart or arter­ies in the brain.”

“Excess and dys­func­tion of adi­pose tis­sue accu­mu­la­tion in the body, both in ani­mals and in humans, are able to increase inflam­ma­tory processes, oxida­tive stress and other things that may have the poten­tial to dis­rupt the lipid metab­o­lism in the liver,” he added, which pre­cip­i­tates chronic kid­ney dis­ease and car­dio­vas­cu­lar dis­or­ders.

“The major objec­tive of our inves­ti­ga­tion was to con­vince the researchers that, in effect, the ben­e­fits obtained with the Mediterranean diet, through extra vir­gin olive oil, were obtained by mod­u­lat­ing these alter­ations,” he said.

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At the end of the study, Nisoli said the research team iden­ti­fied sev­eral sig­nif­i­cant find­ings, paving the way for future stud­ies.

The researchers found that mice fol­low­ing the high-fat diets com­prised of extra vir­gin olive oil could decrease their body weight com­pared to those fol­low­ing the high-fat diet con­tain­ing lard.

They also observed that in all four high-fat diets, only the polyphe­nol-enriched diet demon­strated a sta­tis­ti­cally sig­nif­i­cant reduc­tion in glycemia after eat­ing.

“In addi­tion, we per­formed other mea­sure­ments that demon­strate that mice fed with the diet sub­sti­tuted with extra vir­gin olive oil enriched in polyphe­nols are less insulin resis­tant than high-fat lard diet and the other two extra vir­gin olive oil-enriched diets,” Nisoli said.

“This result is impor­tant to sug­gest that polyphe­nols are effec­tively involved in a nor­mal­iza­tion of glu­cose home­osta­sis and in the poten­tial ben­e­fit in these ani­mals,” he added.

At the end of the exper­i­ment, the researchers extracted tis­sues from the mice to con­duct an RNA sequenc­ing analy­sis that allowed them to mea­sure the gene expres­sion in the mice fed the polyphe­nol-enriched diet com­pared with the other diets.

These com­par­isons allowed the researchers to iden­tify the genes involved in the dif­fer­ent out­comes in the liver and the white adi­pose tis­sues and, more specif­i­cally, see how the con­sump­tion of polyphe­nols cor­re­lated with dif­fer­ent gene expres­sions.

“When you see the same gene increased in the polyphe­nol-enriched high-fat diet com­pared to the polyphe­nol-deprived high-fat diet, you can see that it may be poten­tially involved in the pathol­ogy linked to obe­sity,” Nisoli said. ​“You may demon­strate that polyphe­nols are able to coun­ter­act at least partly the changes caused by obe­sity.”

Based on this obser­va­tion, the researchers con­tin­ued to ana­lyze all the dif­fer­ent genes and con­struct sequences of gene net­works, known as clus­ters, mod­i­fied by the high-fat diet and reverted by the polyphe­nol-enriched diet.

They found that the polyphe­nol-enriched diet decreased the gene expres­sions asso­ci­ated with inflam­ma­tion and oxida­tive stress. Separately, increases in gene expres­sions asso­ci­ated with energy expen­di­ture and mito­chon­dr­ial func­tion were observed in the mice fed the polyphe­nol-enriched diet.

“We con­cluded that if inflam­ma­tion, oxida­tive stress and insulin resis­tance are the cen­tral dam­age caused by car­diometa­bolic syn­drome, polyphe­nol-enriched extra vir­gin olive oil con­sump­tion pre­vents insulin resis­tance sig­nif­i­cantly,” Nisoli said.

“Polyphenols are able to markedly affect gene expres­sion pro­files in diverse meta­bol­i­cally active tis­sues, and in par­tic­u­lar, polyphe­nols seem to pre­vent some of these dam­ages, inflam­ma­tion and oxida­tive stress,” he added.

While Nisoli said these results were promis­ing in researchers’ efforts to define how extra vir­gin olive oil impacts the mol­e­c­u­lar mech­a­nisms behind car­diometa­bolic dis­eases, he said there were some lim­i­ta­tions.

Chief among these could be the dif­fer­ent impacts of extra vir­gin olive oil and polyphe­nol con­sump­tion on gut micro­biota between mice and humans, and he added that plenty of research still needs to be done before researchers can defin­i­tively say how extra vir­gin olive oil impacts the mol­e­c­u­lar mech­a­nisms behind car­diometa­bolic dis­eases.

“This is the begin­ning of the story,” Nisoli con­cluded. ​“We are now try­ing to obtain more infor­ma­tion about the genes that may be involved in the effect of the polyphe­nols. The research will be long.”

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