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Although regulation of fat stores is deemed to be the primary function of leptin, it also plays a role in other physiological processes, as evidenced by its many sites of synthesis other than fat cells, and the many cell types beside hypothalamic cells that have leptin receptors. They reviewed a common polymorphism in the leptin gene A19G; frequency 0. The most recently described eighth mutation reported in January , in a child with Turkish parents, is unique in that it is detected by the standard immunoreactive technique, where leptin levels are elevated; but the leptin does not turn on the leptin receptor, hence the patient has functional leptin deficiency. The placenta produces leptin. My normal weight was Hi John — thanks for sharing your experience. That said, I would definitely suggest using the Nutrisystem counseling service for full clarification, though — especially for questions 2 and 3.

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The most recently described eighth mutation reported in January , in a child with Turkish parents, is unique in that it is detected by the standard immunoreactive technique, where leptin levels are elevated; but the leptin does not turn on the leptin receptor, hence the patient has functional leptin deficiency. A nonsense mutation in the leptin gene that results in a stop codon and lack of leptin production was first observed in mice in In the mouse gene, arginine is encoded by CGA and only requires one nucleotide change to create the stop codon TGA.

The corresponding amino acid in humans is encoded by the sequence CGG and would require two nucleotides to be changed to produce a stop codon, which is much less likely to happen. A recessive frameshift mutation resulting in a reduction of leptin has been observed in two consanguineous children with juvenile obesity. A Human Genome Equivalent HuGE review in looked at studies of the connection between genetic mutations affecting leptin regulation and obesity.

They reviewed a common polymorphism in the leptin gene A19G; frequency 0. They found no association between any of the polymorphisms and obesity. Other rare polymorphisms have been found but their association with obesity are not consistent. A single case of a homozygous transversion mutation of the gene encoding for leptin was reported in January The transversion of c. The mutant leptin could neither bind to nor activate the leptin receptor in vitro , nor in leptin-deficient mice in vivo.

It was found in a two-year-old boy with extreme obesity with recurrent ear and pulmonary infections. Treatment with metreleptin led to "rapid change in eating behavior, a reduction in daily energy intake, and substantial weight loss".

Leptin is produced primarily in the adipocytes of white adipose tissue. Leptin circulates in blood in free form and bound to proteins. Leptin levels vary exponentially, not linearly, with fat mass. In humans, many instances are seen where leptin dissociates from the strict role of communicating nutritional status between body and brain and no longer correlates with body fat levels:.

All known leptin mutations except one are associated with low to undetectable immunoreactive leptin blood levels. The exception is a mutant leptin reported in January which is not functional, but is detected with standard immunoreactive methods.

Predominantly, the "energy expenditure hormone" leptin is made by adipose cells , thus it is labeled fat cell-specific. In the context of its effects , it is important to recognize that the short describing words direct , central , and primary are not used interchangeably.

In regard to the hormone leptin, central vs peripheral refers to the hypothalamic portion of the brain vs non-hypothalamic location of action of leptin; direct vs indirect refers to whether there is no intermediary, or there is an intermediary in the mode of action of leptin; and primary vs secondary is an arbitrary description of a particular function of leptin.

In vertebrates, the nervous system consists of two main parts, the central nervous system CNS and the peripheral nervous system PNS. The primary effect of leptins is in the hypothalamus , a part of the central nervous system.

Leptin receptors are expressed not only in the hypothalamus but also in other brain regions, particularly in the hippocampus. Thus some leptin receptors in the brain are classified as central hypothalamic and some as peripheral non-hypothalamic. Generally, leptin is thought to enter the brain at the choroid plexus , where the intense expression of a form of leptin receptor molecule could act as a transport mechanism.

Increased levels of melatonin causes a downregulation of leptin, [82] however, melatonin also appears to increase leptin levels in the presence of insulin , therefore causing a decrease in appetite during sleeping. Mice with type 1 diabetes treated with leptin or leptin plus insulin, compared to insulin alone had better metabolic profiles: Leptin acts on receptors in the lateral hypothalamus to inhibit hunger and the medial hypothalamus to stimulate satiety.

Thus, a lesion in the lateral hypothalamus causes anorexia due to a lack of hunger signals and a lesion in the medial hypothalamus causes excessive hunger due to a lack of satiety signals. The absence of leptin or its receptor leads to uncontrolled hunger and resulting obesity. Fasting or following a very-low-calorie diet lowers leptin levels.

Leptin binds to neuropeptide Y NPY neurons in the arcuate nucleus in such a way as to decrease the activity of these neurons. Leptin signals to the hypothalamus which produces a feeling of satiety.

Moreover, leptin signals may make it easier for people to resist the temptation of foods high in calories.

The NPY neurons are a key element in the regulation of hunger; small doses of NPY injected into the brains of experimental animals stimulates feeding, while selective destruction of the NPY neurons in mice causes them to become anorexic.

Once leptin has bound to the Ob-Rb receptor, it activates the stat3, which is phosphorylated and travels to the nucleus to effect changes in gene expression, one of the main effects being the down-regulation of the expression of endocannabinoids , responsible for increasing hunger. It modulates the immune response to atherosclerosis, of which obesity is a predisposing factor. Exogenous leptin can promote angiogenesis by increasing vascular endothelial growth factor levels.

Hyperleptinemia produced by infusion or adenoviral gene transfer decreases blood pressure in rats. Leptin microinjections into the nucleus of the solitary tract NTS have been shown to elicit sympathoexcitatory responses, and potentiate the cardiovascular responses to activation of the chemoreflex. In fetal lung, leptin is induced in the alveolar interstitial fibroblasts "lipofibroblasts" by the action of PTHrP secreted by formative alveolar epithelium endoderm under moderate stretch. The leptin from the mesenchyme, in turn, acts back on the epithelium at the leptin receptor carried in the alveolar type II pneumocytes and induces surfactant expression, which is one of the main functions of these type II pneumocytes.

In mice, and to a lesser extent in humans, leptin is required for male and female fertility. Ovulatory cycles in females are linked to energy balance positive or negative depending on whether a female is losing or gaining weight and energy flux how much energy is consumed and expended much more than energy status fat levels. When energy balance is highly negative meaning the woman is starving or energy flux is very high meaning the woman is exercising at extreme levels, but still consuming enough calories , the ovarian cycle stops and females stop menstruating.

Only if a female has an extremely low body fat percentage does energy status affect menstruation. Leptin levels outside an ideal range may have a negative effect on egg quality and outcome during in vitro fertilization.

The placenta produces leptin. Leptin is also expressed in fetal membranes and the uterine tissue. Uterine contractions are inhibited by leptin. Immunoreactive leptin has been found in human breast milk; and leptin from mother's milk has been found in the blood of suckling infant animals.

Leptin along with kisspeptin controls the onset of puberty. Leptin's ability to regulate bone mass was first recognized in Leptin decreases cancellous bone , but increases cortical bone. This "cortical-cancellous dichotomy" may represent a mechanism for enlarging bone size, and thus bone resistance, to cope with increased body weight. Bone metabolism can be regulated by central sympathetic outflow, since sympathetic pathways innervate bone tissue.

Factors that acutely affect leptin levels are also factors that influence other markers of inflammation, e. While it is well-established that leptin is involved in the regulation of the inflammatory response, [] [] [] it has been further theorized that leptin's role as an inflammatory marker is to respond specifically to adipose-derived inflammatory cytokines. In terms of both structure and function, leptin resembles IL-6 and is a member of the cytokine superfamily.

Similar to what is observed in chronic inflammation, chronically elevated leptin levels are associated with obesity, overeating, and inflammation-related diseases, including hypertension , metabolic syndrome , and cardiovascular disease.

While leptin is associated with body fat mass, however, the size of individual fat cells, and the act of overeating, it is interesting that it is not affected by exercise for comparison, IL-6 is released in response to muscular contractions. Thus, it is speculated that leptin responds specifically to adipose-derived inflammation. Taken as such, increases in leptin levels in response to caloric intake function as an acute pro-inflammatory response mechanism to prevent excessive cellular stress induced by overeating.

Thanks for posting a well written, and information overview of this program. I have three questions and maybe one is a question for a NS counselor… 1. Or can tomatoes, cukes, etc. Also, plain or with some sort of dressing? How many turbo shakes can you have per week… and when can they be consumed?

Thanks in advance …. Hi Tami — Thanks for stopping by and taking the time to comment! I always add extra veggies to my greens and have found the only thing you really need to watch out for is the salad dressing.

But for me, cucumbers, tomatoes, etc. I usually have my TurboShake midday — around 2: That said, I would definitely suggest using the Nutrisystem counseling service for full clarification, though — especially for questions 2 and 3. Best of luck if you decide to try the full program!

I wanted to say that this article is nicely written and included almost all the vital info I needed. Thanks for the review. I second your recommendation for Nutrisystem. Their service helped me significantly a few years ago. Hoping for the same results! Hi Maria — thanks for commenting! Hope it goes well again if you decide to give it another try. Have you found that Nutrisystem is a good way for keeping the weight off over the long term?

How long do you really have to be on Nutrisystem before you starting seeing results? Just finished month 1 and lost about 9 pounds! This post could not be written any better! Reading this post reminds me of my good old room mate! He was always trying new weight loss products.

I will forward this page to him. Fairly certain he will have a good read. Thank you for sharing! I just read this well written post. I have a handicapped daughter who has gained so much weight.

We have tried everything with very little success. After taking to her doctors we decided to give NS a try. She started the program on February 16, She is loving the food and the program. She has already dropped three pounds. Her beginning weight was So she has a long way to go. But the support and your post will definitely help her obtain her goals for healthier lifestyle. We will keep you informed on her progress. Thank you so much.

Hi Shirley — What an inspirational story — really hoping she has success! Thanks for keeping us posted, and wishing your daughter all the best. I suppose its ok to use some of your ideas!! I have been on Nutrisystem for about 5 weeks now. I lost 15 pounds the first month and have been following it to a T.

The food tastes fine and it is very easy to just grab something pop it in the microwave if necessary and go. I have been using My Fitness Pal to track my food and am eating about calories a day. The first week was really tough and I had a hard time, but I stuck to it. Now I m satisfied and use to it. Planning on finishing up the second month and then on the 3rd month working in more home cooked meals and tracking to stay at the same calorie level.

Then will switch over to the auto ship of Turbo shakes for my 4th month. I have about 40 pounds to lose and feel like I am making some good headway with the Nutrisystem plan. Good job on the review, very well written.

Wow, nice job Carolyn! Thanks for sharing your story, and best of luck with the rest of your diet. I was very happy to find this website. Just wanted to thank for your time for this wonderful read, and inspirational review!! Hi Kelly — sorry to hear that! Have you tried connecting with the Nutrisystem counseling service?

We had to take Nutrisystem program for 8 weeks because we got it at a discount thru our insurance company. My goal was to loose 30 lbs. At the end of the 8 weeks I had lost only 3 lbs. We did not care for the cardboard like food and did not get anywhere close to our goals.

This program obviously works for lots of folks, but not for us. We did go to the Naturally Slim program and in 8 weeks I lost Naturally Slim is based on not what you eat but when and how you eat and you eat your own real food and got real results. We will stay with our new habits learned with Naturally Slim and will not have any good words from our Nutrisystem experience.

Hi John — thanks for sharing your experience. Thanks so much for sharing your story. It was encouraging and helpful. I am only on my second day of Lean 13 and after comparing the Turbo Shakes with the protein powder I was using before, I noticed that mine was lower in calories, fat, sugar, and carbs and higher in protein by quite a lot.

Thanks again for your review! Hi Peggy — I think you should be fine using your own protein shake. Just to be safe you may want to talk to a Nutrisystem counselor, and they can let you know for sure. The biggest issue would probably be the calorie count of your shake vs. Best of luck with your two weeks. I made some raspberry coffee and chilled it. Thought that might be a nice tip for someone else. Just finished day 1 of the Turbo Takeoff… I was down 2 lbs this morning!!! Yay… only 58 more lbs to go!!!

I am so determined and my mind is in the right place to really do this, this time.. I am very excited for the results.. I know i will be on the program for a few months but, I really feel like I need the structure of this program right now.

I have been feeling a lot of emotions from having gone through breast cancer and several surgeries the last 3 years… I just kinda let myself go… but, I am so ready for this change!!! Thanks for sharing, Lynn! Best of luck with reaching your goals! Very thorough review…thanks for making the decision easier! I just signed up for my first order.

Went with the Core, and really hoping to least a good 20 pounds. Just finished month 1. Does this stuff really work? Thanks for the comment, Heather…It definitely works when you follow the program correctly.

Best of luck if you decide to try it! First, take the time to put the food on a plate like you would normally eat. Focus on the journey. Take the time to praise yourself for the positive change. I started on Nutrisystem exactly 2 months ago with a week lapse. I only wish I had started months before. Question first great info as I really need something kind of no Brainerd and ready.

How long in your experience would you say orders take to turn around? I am currently out of town but want to have the product arrive day if or day after returning so I can hit the ground running.

Thanks ahead for any info. Hi Deb — Thanks for visiting. If I remember correctly, the last time I ordered it only took 3 or 4 days to get my shipment. Thanks for the review! This was helpful in determining which program to start! I also appreciate your thoroughness and videos. I hope to get fit during my weight loss journey and obtain my goal by next year.

Hi Rose — Glad you liked it, and best of luck with your weight loss journey! Is it possible to melt away one to two pounds of stubborn body fat every single day? It sounds insane, but according to the scientific proof — and the thousands who have already done it themselves using this secret — the answer is YES. I have tried every diet on the market. This was my last resort.

In fact, I have to remind myself to get everything in. My doctor is on the program, her husband and son! You need to register to use the tools. The support is mostly in FAQ question-and-answer format with nutrition and exercise advice provided as well. The Nutrisystem tools consist of weight and measurement logs, progress tracker, food diary, meal planner, grocery guide, dining-out guide and an exercise tracker. They also offer live counseling and support services.

Lean Cuisine does not offer meal plans. They offer a full line of frozen dinner products. This does not include snacks, dessert, fresh vegetables or fruits. This does include snacks and dessert, but does not include fresh vegetables or fruits. Video of the Day. Meal Plans Similar to Nutrisystem.

Healthy Choice Compared to Lean Cuisine.

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