LEPTIN Going for the 3 Increases: Increase in Health, Increase in Happiness

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LEPTINGoing for the 3 Increases Increase in
Health, Increase in Happiness Increase in Energy

• Strategies for Success in Weight Management
• By James J. Messina, Ph.D.

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What is Leptin

• About fifty years ago genetic mutation was
  discovered which causes massive obesity in mice
• In 1994 mutation was characterized as an
  inactivation of a specific gene product
• Gene product was subsequently termed leptin (from
  Greek for low-weight) because when product was
  injected into mice they lost weight

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Leptin System
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What is Leptin?

• Leptin was found to be produced in fat cells, so
  amount of leptin in blood is generally
  proportional to weight of person
• Since absence of leptin causes obesity leptin
  itself reduces body fat, it was hypothesized that
  physiological function of leptin was to serve as
  a reporter of degree of body fat

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What is Leptin?

• Broad outlines of physiologic circuit of appetite
  regulation energy expenditure regulated by
  leptin have been mapped
• Leptin levels rise in proportion to adiposity
  (fat cells) but at any given level of adipose
  there is wide variability in concentration of
  plasma leptin
• Leptin levels are elevated in persons with
  obesity insulin resistance

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What research has told us about Leptin

• It was quickly apparent that leptin is generally
  ineffective as signal for excessive body fat,
  since obese people generally have higher, not
  lower, levels of leptin, but yet remain obese
• Probably more important role of leptin is to
  signal to body that body fat has fallen to
  dangerously low levels (for example during
  starvation) thus signal that appropriate
  metabolic changes should occur to preserve
  metabolic resources. This current view of leptin
  was supported by the results of clinical trials
  of leptin on overweight individuals.

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What research has told us about Leptin

• Over 200 candidate genes for obesity-most remain
  unidentified in humans
• Considerable amount of research has focused on
  hypothetical link between obesity type 2
  diabetes in region of leptin receptor gene
• But sequence variations that have been detected
  have not yet been linked to body fat mass

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What we know about Leptin

• Women have higher leptin levels than men, even
  after accounting for estrogen status (e.g., there
  are no consistent differences among premenopausal
  women, postmenopausal women, and postmenopausal
  women on estrogen replacement)
• There is a possibility that testosterone in men
  might have a suppressive effect on production of
  leptin by the adipocyte

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What we know about Leptin- A key factor is body
energy status

• Short-term energy restriction leads to a marked
  fall in circulating leptin levels, even after
  adjusting for changes in adipose mass
• Fall is associated with increased hunger, which
  may be an early impediment to compliance with a
  low-energy diet to achieve weight loss
• While a number of potential signals could mediate
  the acute fall in leptin with energy restriction
• Plasma insulin concentrations decline in parallel
  with leptin levels in this condition

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What we know about Leptin-Dietary Composition

• Dietary composition can affect leptin production
  by the adipocyte
• High-fat diet reduces leptin levels more than a
  high-carbohydrate diet does
• Fructose reduces leptin levels more than glucose
  does
• These findings have obvious implications for the
  relation of dietary composition-specifically
  high-fat diets-to weight gain

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How does Leptin work in Obesity

• Appears that leptin is primarily a signal that is
  active in response to insufficient energy supply
  rather than one that is activated to prevent an
  oversupply of energy
• Apparent ineffectiveness of leptin in obese
  persons despite high circulating levels raises
  questions of whether "leptin resistance" is
  operating in these individuals whether it can
  be overcome to benefit overweight patients

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Latest Research Finding about Leptin

• Researchers have successfully used hormone leptin
  to treat patients suffering from
  lipodystrophy-rare difficult-to-treat disorder
  that shares some characteristics of typical type
  2 diabetes
• People with lipodystrophy have few or no fat
  cells thus lack leptin, a hormone produced by
  stored in fat cells

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Latest Research Finding about Leptin What is
lipodystrophy?

• Because they have no fat cells, people with
  condition usually store huge amounts of lipids
  (fat) in inappropriate places like muscle or
  liver have extremely high levels of lipids in
  their blood
• They are likely to be insulin resistant-meaning
  their bodies don't readily respond to
  insulin-hormone that allows muscle fat cells to
  properly use glucose.

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Another Latest Research Finding

• Establishes a new connection in metabolic
  machinery, tying leptin to crucial pathway in fat
  metabolism in muscle
• Pathway suggests a role for leptin in clearing
  fat out of cells and sheds light on connection
  between diabetes obesity.

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Another Latest Research Finding

• In light of new knowledge about leptin's role in
  fuel metabolism, it makes sense to revisit idea
  of targeting leptin's actions to treat obesity
• Obese people develop resistance to leptin, so
  ability to target downstream pathway bypass
  leptin resistance may be more beneficial than
  treating with leptin itself