Frontiers in Clinical Drug Research-Diabetes and Obesity

Volume: 4

Pharmacological Mechanism of PPARγ Ratio in Diabetes and Obesity

Author(s): Jose Roberto Santin, Marina Jagielski Goss and Nara Lins Meira Quintao

Pp: 199-225 (27)

DOI: 10.2174/9781681084459119040008

* (Excluding Mailing and Handling)

Abstract

The worldwide prevalence of obesity has increased at alarming rates over the last four decades. Overweight and obesity featuring the excess of white adipose tissue are cardiovascular risk conditions consistently associated with the development of complex metabolic disorders, including insulin resistance, type 2 diabetes mellitus ( T2DM) and coronary heart diseases. Many natural and synthetic agonists of peroxisome proliferator-activated receptors (PPARs; nuclear receptors) are used in the treatment of glucose and lipid disorders. PPARs perform different activities, mainly via endogenous ligands produced in the metabolic pathways of fatty acids; and therefore, they are called lipid sensors. PPAR agonists have different properties and specificities for individual PPAR receptor, different absorption/distribution profiles, and distinct gene expression profiles, which ultimately lead to different clinical outcomes. The isoform PPARγ is expressed in white and brown adipose tissue, large intestine and spleen. However, its expression is highest in adipocytes and it plays a key role in the adipogenesis regulation, energy balance and lipid biosynthesis. PPARγ has been the focus of intense research once its ligands have been described to treat T2DM. Some of them are currently prescribed as anti-diabetic drugs, such as thiazolidinedione. PPARγ activation modulates not only insulin sensitization, but also lipid metabolism, vascular tone and inflammation, all processes involved in atherogenesis. Considering the impact of this subject in the public health and the necessity of new approaches for the development of new drugs to treat metabolic diseases and to improve the quality of life, this chapter has the aim of revising important points concerning the involvement of the nuclear receptors in obesity, diabetes and discuss the real possibility of this target to become an effective and safe pharmacological therapy.


Keywords: Adipogenesis, Agonist, Diabetes, Glitazones, Hyperglycaemia, Metabolic syndrome, Nuclear receptors, Obesity, PPARγ, Peroxisome.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
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      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 873362154 and j.to_ip >=873362154 )) and ((j.from_date <= 1740527754 and j.to_date >= 1740527754 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12851) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 873362154 and j.to_ip >=873362154 )) and ((j.from_date <= 1740527754 and j.to_date >= 1740527754 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12851) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 873362154 and j.to_ip >=873362154 )) and ((j.from_date <= 1740527754 and j.to_date >= 1740527754 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12851)
      710μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 2247 and `b`.`banner_from_date` <= 1740527754 and `b`.`banner_to_date` >= 1740527754 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.08msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 2247
      • 3: 1740527754
      • 4: 1740527754
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='e14b2e9a096c879216ae8f6fe5aebb97'
      230μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    10Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        sJZM3Vtdi4iclz4Yl09iGMJGHdYcT1xAHuESMfdZ
        uc_cart_id
        e14b2e9a096c879216ae8f6fe5aebb97
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/12851" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/12851
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6InpiUjExMURHS254WDI4YVpKWVR1d3c9PSIsInZhbHVlIjoiZ0d2UGM1VU45MHJNNnB4YzczTVJ6akJiUThSWHFSTUl0NWU2ZW1xRk1ZYz0iLCJtYWMiOiJlZWMwNDI0ZWY0ZmNiNmY4YjEzY2YzMTRmMDBlN2ViOGY5MTQ4Njc1Yjc5NDM4MjkxODQyNjE0ZTM5OWY2MDQxIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6InpiUjExMURHS254WDI4YVpKWVR1d3c9PSIsInZhbHVlIjoiZ0d2UGM1VU45MHJNNnB4YzczTVJ6akJiUThSWHFSTUl0NWU2ZW1xRk1ZYz0iLCJtYWMiOiJlZWMwNDI0ZWY0ZmNi" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 23:55:54 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjE3LzR3V1p4TjVxdHBNb2ZqMjdSUGc9PSIsInZhbHVlIjoia1JBTVhRblhiRHNRMlh3Y0dxZDNzUmNPQWkwZHlOTnZtSDYwR1A1T1JMSStWOG51Wm41ZUZmN3R1ODI5cVZQUVpXeWo3am56L3YvWEF3eTN3aU9FMXJwa21NNzZMVWVBL1hMSkZWYmI3MG5lbS9Hd1RIRW93MjFhTHo1cURnOFciLCJtYWMiOiJiNjM2YTcxZTVhYjEyN2QwMWE4NGI1OTFlN2Q4ZjliZGUyYzBjNzIzOTdlMDc4NWNmNThmOTAzNTJmNTFmNjE3IiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 11:55:54 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IjE3LzR3V1p4TjVxdHBNb2ZqMjdSUGc9PSIsInZhbHVlIjoia1JBTVhRblhiRHNRMlh3Y0dxZDNzUmNPQWkwZHlOTnZtSDYwR1A1T1JMSStWOG51Wm41ZUZmN3R1ODI5cVZQUVpXeWo3a" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlBXTENzQmYyazlXeVZwTmFBMUZyaUE9PSIsInZhbHVlIjoiVTBQNktlMC8vNi9GN1BvTjBlUzAvT09PcW9FNG9COEVJZ0xRcmgvbnNoRWg1Qy9Nd29zdkZkUnNTeE84RXUxNG4xNS85SDdrMEw5cFEzdlBJT1N4bm5LWE04bjZLWnNyckpYUllPZXdYNXoyOG9nUW5UUEUwWnVIbEdVVm96MUEiLCJtYWMiOiI2N2M4ODZkYWYyN2U3ZjIxYTMyNDY3MWQ5Y2QzZmRhZDkzZThhMDI4YTNlOTIwNDZiOGJiNTU0YmYzYzE2MzFkIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IlBXTENzQmYyazlXeVZwTmFBMUZyaUE9PSIsInZhbHVlIjoiVTBQNktlMC8vNi9GN1BvTjBlUzAvT09PcW9FNG9COEVJZ0xRcmgvbnNoRWg1Qy9Nd29zdkZkUnN" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjE3LzR3V1p4TjVxdHBNb2ZqMjdSUGc9PSIsInZhbHVlIjoia1JBTVhRblhiRHNRMlh3Y0dxZDNzUmNPQWkwZHlOTnZtSDYwR1A1T1JMSStWOG51Wm41ZUZmN3R1ODI5cVZQUVpXeWo3am56L3YvWEF3eTN3aU9FMXJwa21NNzZMVWVBL1hMSkZWYmI3MG5lbS9Hd1RIRW93MjFhTHo1cURnOFciLCJtYWMiOiJiNjM2YTcxZTVhYjEyN2QwMWE4NGI1OTFlN2Q4ZjliZGUyYzBjNzIzOTdlMDc4NWNmNThmOTAzNTJmNTFmNjE3IiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 11:55:54 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IjE3LzR3V1p4TjVxdHBNb2ZqMjdSUGc9PSIsInZhbHVlIjoia1JBTVhRblhiRHNRMlh3Y0dxZDNzUmNPQWkwZHlOTnZtSDYwR1A1T1JMSStWOG51Wm41ZUZmN3R1ODI5cVZQUVpXeWo3a" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlBXTENzQmYyazlXeVZwTmFBMUZyaUE9PSIsInZhbHVlIjoiVTBQNktlMC8vNi9GN1BvTjBlUzAvT09PcW9FNG9COEVJZ0xRcmgvbnNoRWg1Qy9Nd29zdkZkUnNTeE84RXUxNG4xNS85SDdrMEw5cFEzdlBJT1N4bm5LWE04bjZLWnNyckpYUllPZXdYNXoyOG9nUW5UUEUwWnVIbEdVVm96MUEiLCJtYWMiOiI2N2M4ODZkYWYyN2U3ZjIxYTMyNDY3MWQ5Y2QzZmRhZDkzZThhMDI4YTNlOTIwNDZiOGJiNTU0YmYzYzE2MzFkIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IlBXTENzQmYyazlXeVZwTmFBMUZyaUE9PSIsInZhbHVlIjoiVTBQNktlMC8vNi9GN1BvTjBlUzAvT09PcW9FNG9COEVJZ0xRcmgvbnNoRWg1Qy9Nd29zdkZkUnN" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "sJZM3Vtdi4iclz4Yl09iGMJGHdYcT1xAHuESMfdZ" "uc_cart_id" => "e14b2e9a096c879216ae8f6fe5aebb97" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/12851" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 23:55:54GET/chapter/128511121912