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Metabolic consequences of a Paleolithic diet in obese postmenopausal women
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. (Tommy Olsson)ORCID iD: 0000-0001-9496-8087
2017 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Metabola konsekvenser av en paleolitisk kost hos postmenopausal kvinnor med fetma (Swedish)
Abstract [en]

Background

Obesity, in particular abdominal adiposity, is associated with elevated fatty acids and pro-inflammatory adipokines, which are linked to ectopic fat storage and insulin resistance. During menopause, there is a redistribution of fat from the peripheral to abdominal depots. This transition is associated with an increased risk of type 2 diabetes and cardiovascular diseases. We hypothesized that a Paleolithic diet, with high proportions of lean meat, fish, vegetables, fruits, and oils, but devoid of dairy products and cereals, might have long-term beneficial effects on inflammation, fat metabolism, and circulating fatty acids. These effects might potentially reduce the risk of metabolic complications in postmenopausal women that are obese.

 Methods

Postmenopausal women with obesity were studied before, after six months, and after 24 months of one of two specified ad libitum diets. One diet was a Paleolithic diet, in which approximately 30% of the total energy (E%) was protein, 30 E% was fat, and 40 E% was carbohydrate. The other diet was a prudent control diet, consistent with Nordic Nutrition recommendations of 15 E% protein, 25 E% fat, and 55 E% carbohydrate. Dietary intakes of polyunsaturated fatty acids and protein were validated objectively by measuring circulating and urinary biomarkers. Anthropometrics and diet reports were analyzed, and abdominal subcutaneous fat samples were evaluated for the expression of proteins key in inflammation and fat metabolism and for lipoprotein lipase mass and activity. In addition, blood samples were analyzed to determine concentrations of specific serum proteins, serum lipids, and the fatty acids carried in cholesterol esters.

Results

The Paleolithic diet group reported reduced intakes of saturated fatty acids and carbohydrates and elevated intakes of protein and unsaturated fatty acids, compared to baseline. The elevated intakes of polyunsaturated fatty acids and protein were objectively verified for this group. After 24 months, both diets were found to have beneficial effects on the expression of inflammation-related genes in adipose tissue and pro-inflammatory factors in the circulation. Compared to the control group, the Paleolithic diet group exhibited more pronounced reductions of circulating cardiometabolic risk factors, including the ratio of triglycerides to high density lipoprotein, lipogenic index, specific fatty acids, and indices of desaturase activities. After six months, the Paleolithic group also exhibited more pronounced reductions in lipogenesis-promoting factors, including the expression of key proteins in fat synthesis, the activity of lipoprotein lipase, and the activity of stearoyl-CoA desaturase 1, compared to the control group.

Conclusion

Long-term weight loss in postmenopausal obese women was accompanied by reductions in low-grade inflammation in adipose tissue and in the circulation. In addition, a Paleolithic diet, with a high content of unsaturated fatty acids and a low content of refined carbohydrates, appeared to provide greater reductions in cardiometabolic risk factors associated with insulin resistance and lipogenesis, compared to a prudent control diet.

 

Abstract [sv]

Bakgrund

De senaste decennierna har förekomsten av övervikt och fetma ökat kraftigt i stora delar av världen. Detta beror på en kombination av olika faktorer såsom specifika gener vilka främjar fettinlagring, men kanske främst ett överintag av energirik mat i kombination med minskad fysisk aktivitet. Fetma och specifikt bukfetma, vilket tilltar hos kvinnor efter klimakteriet (postmenopausala), ökar risken för höjda blodfettsnivåer och låggradig inflammation, vilket kan leda till utveckling av typ 2-diabetes samt hjärt- och kärlsjukdomar. Kost och viktnedgång är avgörande för bibehållen hälsa och av stort intresse är att urbefolkningar runt om i världen har låg förekomst av fetma, diabetes, hjärt- och kärlsjukdom, troligtvis kopplat till olika livsstilsfaktorer som högre fysisk aktivitet samt kostfaktorer. 

Syfte

Vårt syfte var att undersöka metabola förändringar i fettväv och cirkulation hos postmenopausala kvinnor med fetma kopplat till en 24 månaders paleolitisk kostintervention. Den paleolitiska kosten, som ingick i studien består av en hög andel magert kött, fisk, grönsaker, frukt, nötter, oliv- och rapsolja och där mjölkprodukter och spannmål är uteslutna. Vår hypotes var att en paleolitisk kost med hög andel protein och omättade fettsyror har fördelaktiga långtidseffekter på inflammation, fettmetabolism och cirkulerande fettsyror jämfört med en kost baserad på Nordiska näringsrekommendationer med ett högt intag av kolhydrater.

Metoder

Postmenopausala kvinnor med fetma studerades före, vid sex månader och efter 24 månaders intag, utan energirestriktioner, av antingen en paleolitisk kost eller en kost enligt Nordiska näringsrekommendationer. Kroppsmätningar, kostregistreringar, genuttryck av nyckelproteiner i inflammation och fettmetabolism i fettväv samt koncentrationer av blodfetter, specifika proteiner och fettsyror bestämdes i plasma.

Resultat

I linje med rekommendationerna så rapporterade gruppen som åt den paleolitiska kosten ett minskat intag av mättat fett och kolhydrater samt ett ökat intag av protein och omättat fett jämfört med baslinjenivåerna. Det ökade intaget av fleromättade fettsyror och protein bekräftades med objektiva mätmetoder. Efter 24 månaders intervention uppvisade båda grupperna en jämförbar viktnedgång och en minskning av flertalet proinflammatoriska faktorer i såväl fettväv som i cirkulation. Den grupp som åt paleolitisk kost uppvisade en kraftigare reduktion av cirkulerande kardiometabola riskfaktorer som index för fettsyntes och desaturaser, specifika fettsyror samt kvoten triglycerider till HDL (high density lipoprotein). Efter sex månader bidrog den paleolitiska kosten också till en mer påtaglig minskning av faktorer involverade i fettinlagring, som uttryck av specifika nyckelproteiner i fettsyntes, aktivitet för lipoprotein lipas och stearoyl-CoA desaturase 1 index jämfört med kontrollkosten.

Slutsatser

En långvarig viktminskning hos postmenopausala kvinnor med fetma åtföljs av en minskad låggradig inflammation i fettväv och i cirkulation. En paleolitisk kost med hög andel omättade fettsyror och låga halt kolhydrater är kopplat till en kraftigare minskning av riskparametrar för insulinresistens och nyckelfaktorer för fettinlagring jämfört med en kontrollkost enligt Nordiska näringsrekommendationer.

Place, publisher, year, edition, pages
Umeå: Umeå University , 2017. , p. 59
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1937
Keyword [en]
Postmenopausal women, Paleolithic diet, randomized diet intervention, fat metabolism, low-grade inflammation, circulating fatty acids, diet validation, obesity, insulin resistance
Keyword [sv]
Postmenopausala kvinnor, Paleolitisk kost, randomiserad kostintervention, fettmetabolism, fetma, låggradig inflammation, cirkulerande fettsyror, kostvalidering, fetma, insulin resistens
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:umu:diva-143133ISBN: 978-91-7601-795-1 (print)OAI: oai:DiVA.org:umu-143133DiVA, id: diva2:1167926
Public defence
2017-01-26, Triple helix, Samverkanshuset, Universitetstorget 4, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Funder
Swedish Heart Lung Foundation, 20130684Swedish Research Council, 12237Swedish Research Council, 2015-02942Forte, Swedish Research Council for Health, Working Life and Welfare, 2006-0699Västerbotten County Council
Available from: 2017-12-21 Created: 2017-12-19 Last updated: 2017-12-21Bibliographically approved
List of papers
1. Decreased lipogenesis-promoting factors in adipose tissue in postmenopausal women with overweight on a Paleolithic-type diet
Open this publication in new window or tab >>Decreased lipogenesis-promoting factors in adipose tissue in postmenopausal women with overweight on a Paleolithic-type diet
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2017 (English)In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215Article in journal (Refereed) Epub ahead of print
Abstract [en]

Purpose: We studied effects of diet-induced postmenopausal weight loss on gene expression and activity of proteins involved in lipogenesis and lipolysis in adipose tissue.

Methods: Fifty-eight postmenopausal women with overweight (BMI 32.5 ± 5.5) were randomized to eat an ad libitum Paleolithic-type diet (PD) aiming for a high intake of protein and unsaturated fatty acids or a prudent control diet (CD) for 24 months. Anthropometry, plasma adipokines, gene expression of proteins involved in fat metabolism in subcutaneous adipose tissue (SAT) and lipoprotein lipase (LPL) activity and mass in SAT were measured at baseline and after 6 months. LPL mass and activity were also measured after 24 months.

Results: The PD led to improved insulin sensitivity (P < 0.01) and decreased circulating triglycerides (P < 0.001), lipogenesis-related factors, including LPL mRNA (P < 0.05), mass (P < 0.01), and activity (P < 0.001); as well as gene expressions of CD36 (P < 0.05), fatty acid synthase, FAS (P < 0.001) and diglyceride acyltransferase 2, DGAT2 (P < 0.001). The LPL activity (P < 0.05) and gene expression of DGAT2 (P < 0.05) and FAS (P < 0.05) were significantly lowered in the PD group versus the CD group at 6 months and the LPL activity (P < 0.05) remained significantly lowered in the PD group compared to the CD group at 24 months.

Conclusions: Compared to the CD, the PD led to a more pronounced reduction of lipogenesis-promoting factors in SAT among postmenopausal women with overweight. This could have mediated the favorable metabolic effects of the PD on triglyceride levels and insulin sensitivity.

Place, publisher, year, edition, pages
Springer, 2017
Keyword
diet, fat metabolism, lipoprotein lipase, obesity, postmenopausal women
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-141559 (URN)10.1007/s00394-017-1558-0 (DOI)29075849 (PubMedID)
Available from: 2017-11-08 Created: 2017-11-08 Last updated: 2017-12-19
2. Attenuated Low-Grade Inflammation Following Long-Term Dietary Intervention in Postmenopausal Women with Obesity
Open this publication in new window or tab >>Attenuated Low-Grade Inflammation Following Long-Term Dietary Intervention in Postmenopausal Women with Obesity
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2017 (English)In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 25, no 5, p. 892-900Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Abdominal fat accumulation after menopause is associated with low-grade inflammation and increased risk of metabolic disorders. Effective long-term lifestyle treatment is therefore needed.

METHODS: Seventy healthy postmenopausal women (age 60 ± 5.6 years) with BMI 32.5 ± 5.5 were randomized to a Paleolithic-type diet (PD) or a prudent control diet (CD) for 24 months. Blood samples and fat biopsies were collected at baseline, 6 months, and 24 months to analyze inflammation-related parameters.

RESULTS: Android fat decreased significantly more in the PD group (P = 0.009) during the first 6 months with weight maintenance at 24 months in both groups. Long-term significant effects (P < 0.001) on adipose gene expression were found for toll-like receptor 4 (decreased at 24 months) and macrophage migration inhibitory factor (increased at 24 months) in both groups. Serum interleukin 6 (IL-6) and tumor necrosis factor α levels were decreased at 24 months in both groups (P < 0.001) with a significant diet-by-time interaction for serum IL-6 (P = 0.022). High-sensitivity C-reactive protein was decreased in the PD group at 24 months (P = 0.001).

CONCLUSIONS: A reduction of abdominal obesity in postmenopausal women is linked to specific changes in inflammation-related adipose gene expression.

National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-134986 (URN)10.1002/oby.21815 (DOI)000400045000013 ()28440046 (PubMedID)
Funder
Swedish Research Council, K2011-12237-15-6
Available from: 2017-05-15 Created: 2017-05-15 Last updated: 2018-01-11Bibliographically approved
3. Long-term effects of a Paleolithic diet on plasma fatty acid composition in postmenopausal women with obesity: a randomized trial
Open this publication in new window or tab >>Long-term effects of a Paleolithic diet on plasma fatty acid composition in postmenopausal women with obesity: a randomized trial
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: A Paleolithic-type diet (PD) can improve cardiometabolic risk factors, but its impact on plasma fatty acid (FA) composition is unknown. We hypothesized that a PD improves dietary fat quality and FA metabolism, which may help counteract obesity-related metabolic dysfunction. 

Objective: The current study investigated the impact of a PD on biomarkers of dietary fat quality and indices of FA desaturation and de novo lipogenesis compared with a prudent control diet (CD).

Design: This randomized 2-year trial included 70 women (mean ± SD age 60 ± 5.6 years, BMI 33 ± 3.4). The PD was rich in fish and vegetable fats but devoid of dairy products and lower in carbohydrates than the CD advised to follow the Nordic Nutrition recommendations. FA composition of plasma cholesterol esters (CE) was assessed using gas chromatography, desaturase activities estimated by product-to-precursor FA ratios, and dietary intake measured by 4-day food records at baseline and after 6 and 24 months.

Results: Saturated fat (P=0.009) and carbohydrate (P<0.001) intake was lower, whereas polyunsaturated (PUFA), monounsaturated FA, and protein intake were higher at 24 after PD versus CD (all P<0.001). Changes in plasma FA composition during PD compared to CD suggested that saturated FAs from dairy foods were partly replaced with PUFAs from fish and vegetable sources. Although comparable BMI, energy intake, and physical activity were found at 24 months with both diets, metabolic markers and desaturase activity indices, including 16:0 (P=0.005), 16:1n-7 (P=0.002), 20:3n-6 (P=0.004), stearoyl-CoA desaturase 1 (SCD-1) (P=0.006), lipogenic index (P<0.001), and the triglyceride/high-density lipoprotein cholesterol ratio (P=0.031), were lower after 24 months of PD versus CD.

Conclusions: The PD had long-term effects on dietary fat quality intake and plasma FA composition, changes previously linked to improved cardiometabolic health. The results may suggest an anti-lipogenic effect of PD, possibly contributing to improved dyslipidemia.

Keyword
Paleolithic diet, postmenopausal women, circulating fatty acids, desaturase activities, validation of diet intake
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-143256 (URN)
Available from: 2017-12-19 Created: 2017-12-19 Last updated: 2017-12-20

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