1. Översiktlig projektbeskrivning

Engelsk titel

The impact of human adipose tissue cellularity in obesity and metabolic disease - focus on type 2 diabetes, ectopic fat accumulation and polycystic ovary syndrome

Sammanfattning av projektet

Övergripande fråga: Varför löper feta individer med stora fettceller (adipocyter) högre risk att utveckla typ 2 diabetes än feta individer, med samma mängd kroppsfett, men med mindre fettceller?
Bakgrund: Fetma, i synnerhet bukfetma, är kopplad till typ 2 diabetes, hjärt-kärlsjukdom och polycystiskt ovariesyndrom (PCOS). Inte bara mängden fettvävnad, och placeringen av den på kroppen, utan även fettcellernas storlek är en riskfaktor för metabol sjukdom men orsaken till detta är oklar. Stora adipocyter kan bl a vara kopplade till inflammation och ektopisk lagring av fett inne i buken (visceralt fett), i lever och muskulatur.
Syfte: Att definiera de mekanismer som länkar adipocytstorlek till metabol sjukdom, och detektera gener som är involverade vid utveckling av PCOS, med långsiktigt mål att förbättra möjligheter att förebygga och behandla.
Arbetsplan: Studera adipocytstorlek och inflammatoriska markörer, genexpression och metabolism, i adipocyter och fettvävnad från feta patienter och kvinnor med PCOS, före och efter behandling. Bestämning av ektopiskt fett hos feta patienter (magnetisk resonansspektroskopi), och i små lever- och muskelbiopsier (CARS mikroskopi). Mängd ektopiskt fett relateras till adipocytstorlek i subkutan och visceral depå och till patienternas metabola/immunologiska status. Med en rått-modell för PCOS och en strategi för detektion av specifika gener studeras gener som är involverade vid utveckling av PCOS.

Typ av projekt

Forskningsprojekt

MeSH-termer för att beskriva ämnesområdet

Inlagda MeSH-termer

Overweight

A status with BODY WEIGHT that is above certain standard of acceptable or desirable weight. In the scale of BODY MASS INDEX, overweight is defined as having a BMI of 25.0-29.9 kg/m2. Overweight may or may not be due to increases in body fat (ADIPOSE TISSUE), hence overweight does not equal "over fat".

Body Weights and Measures

Measurements of the height, weight, length, area, etc., of the human and animal body or its parts.

Body Weight

The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.

Obesity

A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).

Obesity, Morbid

The condition of weighing two, three, or more times the ideal weight, so called because it is associated with many serious and life-threatening disorders. In the BODY MASS INDEX, morbid obesity is defined as having a BMI greater than 40.0 kg/m2.

Diabetes Mellitus, Type 2

A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.

Glucose Metabolism Disorders

Pathological conditions in which the BLOOD GLUCOSE cannot be maintained within the normal range, such as in HYPOGLYCEMIA and HYPERGLYCEMIA. Etiology of these disorders varies. Plasma glucose concentration is critical to survival for it is the predominant fuel for the CENTRAL NERVOUS SYSTEM.

Metabolic Diseases

Generic term for diseases caused by an abnormal metabolic process. It can be congenital due to inherited enzyme abnormality (METABOLISM, INBORN ERRORS) or acquired due to disease of an endocrine organ or failure of a metabolically important organ such as the liver. (Stedman, 26th ed)

Endocrine System Diseases

Pathological processes of the ENDOCRINE GLANDS, and diseases resulting from abnormal level of available HORMONES.

Polycystic Ovary Syndrome

A complex disorder characterized by infertility, HIRSUTISM; OBESITY; and various menstrual disturbances such as OLIGOMENORRHEA; AMENORRHEA; ANOVULATION. Polycystic ovary syndrome is usually associated with bilateral enlarged ovaries studded with atretic follicles, not with cysts. The term, polycystic ovary, is misleading.

Adipose Tissue

Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.

Intra-Abdominal Fat

Fatty tissue inside the ABDOMINAL CAVITY, including visceral fat and retroperitoneal fat. It is the most metabolically active fat in the body and easily accessible for LIPOLYSIS. Increased visceral fat is associated with metabolic complications of OBESITY.

Adipose Tissue, White

Fatty tissue composed of WHITE ADIPOCYTES and generally found directly under the skin (SUBCUTANEOUS FAT) and around the internal organs (ABDOMINAL FAT). It has less vascularization and less coloration than the BROWN FAT. White fat provides heat insulation, mechanical cushion, and source of energy.

Adiposity

The amount of fat or lipid deposit at a site or an organ in the body, an indicator of body fat status.

Body Fat Distribution

Deposits of ADIPOSE TISSUE throughout the body. The pattern of fat deposits in the body regions is an indicator of health status. Excess ABDOMINAL FAT increases health risks more than excess fat around the hips or thighs, therefore, WAIST-HIP RATIO is often used to determine health risks.

Projektets delaktighet i utbildning

Avhandling
D-uppsats / Magisterexamen
C-uppsats / Kandidatexamen
ST-läkarutbildning
Annan utbildning
Ej del i utbildning

3. Processen och projektets redovisning

Pågående aktiviteter

Planering och förberedelse före datainsamling
Datainsamling pågår
Analys av insamlade data pågår
Författande av skriftlig redovisning / publikation pågår
En eller flera publikationer från projektet är publicerade
Slutfört och inget mer görs inom ramen för detta projekt

Projektstart (när planeringen påbörjas och börjar dokumenteras skriftligt)

2007-07-01

Publikationer från detta projekt

1. Coagulation and fibrinolytic disturbances in women with polycystic ovary syndrome.

   Mannerås-Holm Louise, Baghaei Fariba, Holm Göran, Janson Per Olof, Ohlsson Claes, Lönn Malin, Stener-Victorin Elisabet.

   J Clin Endocrinol Metab. 2011:96(4):1068-76.

   [Links: PMID: 21252248 | DOI länk][Source: PubMed®]
2. Adipose Tissue Has Aberrant Morphology and Function in PCOS: Enlarged Adipocytes and Low Serum Adiponectin, But Not Circulating Sex Steroids, Are Strongly Associated with Insulin Resistance.

   Mannerås-Holm Louise, Leonhardt Henrik, Kullberg Joel, Jennische Eva, Odén Anders, Holm Göran, Hellström Mikael, Lönn Lars, Olivecrona Gunilla, Stener-Victorin Elisabet, Lönn Malin.

   J Clin Endocrinol Metab. 2011:96(2):E304-11.

   [Links: PMID: 21084397 | DOI länk][Source: PubMed®]
3. Beneficial metabolic effects of the Malaysian herb Labisia pumila var. alata in a rat model of polycystic ovary syndrome.

   Mannerås L, Fazliana M, Wan Nazaimoon W M, Lönn M, Gu H F, Ostenson C G, Stener-Victorin E.

   J Ethnopharmacol 2010:127(2):346-51.

   [Links: PMID: 19883744 | DOI länk][Source: PubMed®]
4. Adipocyte size predicts incidence of type 2 diabetes in women.

   Lönn Malin, Mehlig Kirsten, Bengtsson Calle, Lissner Lauren.

   FASEB J. 2010:24(1):326-31.

   [Links: PMID: 19741173 | DOI länk][Source: PubMed®]
5. Acupuncture and exercise restore adipose tissue expression of sympathetic markers and improve ovarian morphology in rats with dihydrotestosterone-induced PCOS.

   Mannerås Louise, Cajander Stefan, Lönn Malin, Stener-Victorin Elisabet.

   Am J Physiol Regul Integr Comp Physiol. 2009:296(4):R1124-31.

   [Links: PMID: 19158405 | DOI länk][Source: PubMed®]
6. Influence of herring (Clupea harengus) and herring fractions on metabolic status in rats fed a high energy diet.

   Lindqvist H, Sandberg A-S, Undeland I, Stener-Victorin E, Larsson B M, Sannaveerappa T, Lönn M, Holmäng A.

   Acta Physiol (Oxf) 2009:196(3):303-14.

   [Links: PMID: 19076113 | DOI länk][Source: PubMed®]
7. Heterogeneous glycosylation patterns of human PAI-1 may reveal its cellular origin.

   Brogren Helén, Sihlbom Carina, Wallmark Karin, Lönn Malin, Deinum Johanna, Karlsson Lena, Jern Sverker.

   Thromb Res. 2008:122(2):271-81.

   [Links: PMID: 18508114 | DOI länk][Source: PubMed®]
8. Low-frequency electro-acupuncture and physical exercise improve metabolic disturbances and modulate gene expression in adipose tissue in rats with dihydrotestosterone-induced polycystic ovary syndrome.

   Mannerås Louise, Jonsdottir Ingibjörg H, Holmäng Agneta, Lönn Malin, Stener-Victorin Elisabet.

   Endocrinology 2008:149(7):3559-68.

   [Links: PMID: 18388196 | DOI länk][Source: PubMed®]
9. Stora fettceller kan öka risken för utveckling av typ 2-diabetes.

   Lönn M, Lissner L.

   Läkartidningen 2009:106:3068.

   [Links: pdf][Source: User]